NM_001243156.2:c.1489G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001243156.2(TAF1C):c.1489G>A(p.Gly497Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,595,058 control chromosomes in the GnomAD database, including 443 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 37 hom., cov: 33)

Exomes 𝑓: 0.020 ( 406 hom. )

Consequence

TAF1C
NM_001243156.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.542

Publications

23 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025316477).

BP6

Variant 16-84180078-C-T is Benign according to our data. Variant chr16-84180078-C-T is described in ClinVar as Benign. ClinVar VariationId is 3068683.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2 link	c.1489G>A	p.Gly497Arg	missense_variant	Exon 14 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.1489G>A	p.Gly497Arg	missense_variant	Exon 14 of 15	2	NM_001243156.2	ENSP00000455933.1		Q15572-6

Frequencies

GnomAD3 genomes

AF:

0.0157

AC:

2393

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00847

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0316

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0199

Gnomad OTH

AF:

0.0206

GnomAD2 exomes

AF:

0.0194

AC:

4318

AN:

222282

AF XY:

0.0209

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0409

Gnomad EAS exome

AF:

0.000174

Gnomad FIN exome

AF:

0.00455

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0200

AC:

28790

AN:

1442766

Hom.:

406

Cov.:

AF XY:

0.0207

AC XY:

14872

AN XY:

716934

show subpopulations

African (AFR)

AF:

0.00807

AC:

266

AN:

32962

American (AMR)

AF:

0.0136

AC:

568

AN:

41876

Ashkenazi Jewish (ASJ)

AF:

0.0423

AC:

1035

AN:

24496

East Asian (EAS)

AF:

0.000202

AC:

AN:

39654

South Asian (SAS)

AF:

0.0372

AC:

3094

AN:

83194

European-Finnish (FIN)

AF:

0.00542

AC:

277

AN:

51072

Middle Eastern (MID)

AF:

0.0712

AC:

402

AN:

5650

European-Non Finnish (NFE)

AF:

0.0198

AC:

21836

AN:

1104312

Other (OTH)

AF:

0.0219

AC:

1304

AN:

59550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.0157

AC:

2385

AN:

152292

Hom.:

Cov.:

AF XY:

0.0154

AC XY:

1150

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00844

AC:

351

AN:

41572

American (AMR)

AF:

0.0154

AC:

236

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0427

AC:

148

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0315

AC:

152

AN:

4832

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0199

AC:

1354

AN:

67998

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

124

248

371

495

619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0203

Hom.:

183

Bravo

AF:

0.0156

TwinsUK

AF:

0.0175

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.00418

AC:

ESP6500EA

AF:

0.0184

AC:

156

ExAC

AF:

0.0184

AC:

2221

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Complex neurodevelopmental disorder

Benign:1

May 04, 2023

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

South Asian population allele frequency is 3.735% (rs4150167, 1059/26938 alleles, 75 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.2.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

.;.;T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.74

T;T;T;T;.

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;L;.;.

PhyloP100

0.54

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.7

.;N;N;N;N

REVEL

Benign

0.044

Sift

Uncertain

0.0060

.;D;T;T;T

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.98, 0.99

.;D;D;D;.

Vest4

0.11

MutPred

0.31

.;.;Gain of solvent accessibility (P = 0.0014);.;.;

ClinPred

0.011

GERP RS

1.3

Varity_R

0.081

gMVP

0.54

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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