16-84179828-A-T

Variant summary

Our verdict is Benign. Variant got -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. 14/19 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

18

Clinical Significance

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

Conservation

PhyloP100: -1.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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
TAF1CNM_001243156.2 linkc.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
TAF1CENST00000566732.6 linkc.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.:
32
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
GnomAD3 exomes
AF:
0.397
AC:
93925
AN:
236712
Hom.:
19272
AF XY:
0.393
AC XY:
51298
AN XY:
130492
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 SAS exome
AF:
0.324
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.:
84
AF XY:
0.401
AC XY:
289940
AN XY:
722664
show subpopulations
Gnomad4 AFR exome
AF:
0.190
Gnomad4 AMR exome
AF:
0.516
Gnomad4 ASJ exome
AF:
0.380
Gnomad4 EAS exome
AF:
0.379
Gnomad4 SAS exome
AF:
0.323
Gnomad4 FIN exome
AF:
0.382
Gnomad4 NFE exome
AF:
0.416
Gnomad4 OTH exome
AF:
0.386
GnomAD4 genome
AF:
0.348
AC:
52859
AN:
151890
Hom.:
9945
Cov.:
32
AF XY:
0.349
AC XY:
25939
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.201
Gnomad4 AMR
AF:
0.440
Gnomad4 ASJ
AF:
0.380
Gnomad4 EAS
AF:
0.371
Gnomad4 SAS
AF:
0.323
Gnomad4 FIN
AF:
0.386
Gnomad4 NFE
AF:
0.407
Gnomad4 OTH
AF:
0.357
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:2
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

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.73
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
3.0
DANN
Benign
0.95
DEOGEN2
Benign
0.0025
.;.;T;.;.
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.31
T;T;T;T;.
MetaRNN
Benign
0.00013
T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.69
.;.;N;.;.
PrimateAI
Benign
0.29
T
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
T
GERP RS
1.2
Varity_R
0.053
gMVP
0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2230129; hg19: chr16-84213434; COSMIC: COSV58985280; COSMIC: COSV58985280; API