16-84179828-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001243156.2(TAF1C):c.1645T>A(p.Leu549Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,606,516 control chromosomes in the GnomAD database, including 130,400 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9945 hom., cov: 32)

Exomes 𝑓: 0.40 ( 120455 hom. )

Consequence

TAF1C
NM_001243156.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.50

Publications

37 publications found

Variant links:

Genes affected

TAF1C (HGNC:11534): (TATA-box binding protein associated factor, RNA polymerase I subunit C) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2011]

TAF1C Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

TAF1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2755394E-4).

BP6

Variant 16-84179828-A-T is Benign according to our data. Variant chr16-84179828-A-T is described in ClinVar as Benign. ClinVar VariationId is 402596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2 link	c.1645T>A	p.Leu549Met	missense_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2	Q15572-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6 link	c.1645T>A	p.Leu549Met	missense_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1		Q15572-6

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52821

AN:

151772

Hom.:

9930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.201

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.386

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.362

GnomAD2 exomes

AF:

0.397

AC:

93925

AN:

236712

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.526

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.408

GnomAD4 exome

AF:

0.404

AC:

587698

AN:

1454626

Hom.:

120455

Cov.:

AF XY:

0.401

AC XY:

289940

AN XY:

722664

show subpopulations

African (AFR)

AF:

0.190

AC:

6358

AN:

33388

American (AMR)

AF:

0.516

AC:

22758

AN:

44142

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

9880

AN:

26010

East Asian (EAS)

AF:

0.379

AC:

14993

AN:

39532

South Asian (SAS)

AF:

0.323

AC:

27745

AN:

86008

European-Finnish (FIN)

AF:

0.382

AC:

19753

AN:

51758

Middle Eastern (MID)

AF:

0.392

AC:

2256

AN:

5748

European-Non Finnish (NFE)

AF:

0.416

AC:

460786

AN:

1107992

Other (OTH)

AF:

0.386

AC:

23169

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

24217

48435

72652

96870

121087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14238

28476

42714

56952

71190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.348

AC:

52859

AN:

151890

Hom.:

9945

Cov.:

AF XY:

0.349

AC XY:

25939

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.201

AC:

8320

AN:

41440

American (AMR)

AF:

0.440

AC:

6721

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1319

AN:

3470

East Asian (EAS)

AF:

0.371

AC:

1900

AN:

5128

South Asian (SAS)

AF:

0.323

AC:

1555

AN:

4810

European-Finnish (FIN)

AF:

0.386

AC:

4074

AN:

10568

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27654

AN:

67888

Other (OTH)

AF:

0.357

AC:

754

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1692

3383

5075

6766

8458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.383

Hom.:

3775

Bravo

AF:

0.351

TwinsUK

AF:

0.423

AC:

1567

ALSPAC

AF:

0.417

AC:

1609

ESP6500AA

AF:

0.173

AC:

693

ESP6500EA

AF:

0.380

AC:

2966

ExAC

AF:

0.381

AC:

45197

Asia WGS

AF:

0.310

AC:

1077

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Thalidomide response

Other:1

Rare Diseases Genetics and Genomics, Islamia College Peshawar

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:research

this variant was associated with excellent response to thalidomide (achieving transfusion independence) excellent responsive

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.0

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0025

.;.;T;.;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.31

T;T;T;T;.

MetaRNN

Benign

0.00013

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

.;.;N;.;.

PhyloP100

-1.5

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.18

.;N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.14

.;T;T;T;T

Sift4G

Benign

0.27

T;T;T;T;T

Polyphen

0.90

.;P;P;P;.

Vest4

0.067

ClinPred

0.0070

GERP RS

1.2

Varity_R

0.053

gMVP

0.25

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over