rs4150167

Positions:

• chr16-84180078-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 12/19 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.542

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
TAF1C	NM_001243156.2	c.1489G>A	p.Gly497Arg	missense_variant	14/15	ENST00000566732.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF1C	ENST00000566732.6	c.1489G>A	p.Gly497Arg	missense_variant	14/15	2	NM_001243156.2	P2

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2393 AN: 152174 Hom.: 38 Cov.: 33

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

GnomAD3 exomes AF: 0.0194 AC: 4318 AN: 222282 Hom.: 88 AF XY: 0.0209 AC XY: 2555 AN XY: 122090

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 SAS exome AF: 0.0393

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.: 75 AF XY: 0.0207 AC XY: 14872 AN XY: 716934

Gnomad4 AFR exome AF: 0.00807

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0423

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.0372

Gnomad4 FIN exome AF: 0.00542

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0219

GnomAD4 genome AF: 0.0157 AC: 2385 AN: 152292 Hom.: 37 Cov.: 33 AF XY: 0.0154 AC XY: 1150 AN XY: 74456

Gnomad4 AFR AF: 0.00844

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.00377

Gnomad4 NFE AF: 0.0199

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0219 Hom.: 97

Bravo AF: 0.0156

TwinsUK AF: 0.0175 AC: 65

ALSPAC AF: 0.0197 AC: 76

ESP6500AA AF: 0.00418 AC: 18

ESP6500EA AF: 0.0184 AC: 156

ExAC AF: 0.0184 AC: 2221

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Complex neurodevelopmental disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

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	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;.;T;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.74	T;T;T;T;.
MetaRNN	Benign	0.0025	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;.;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.50	T
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	T
GERP RS		1.3
Varity_R		0.081
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs4150167; hg19: chr16-84213684;