16-84179132-C-T

Variant names:

• chr16-84179132-C-T
• rs148942327
• NM_001243156.2:c.2341G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001243156.2(TAF1C):​c.2341G>A​(p.Val781Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,608,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V781L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: TAF1C NM_001243156.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 1 publications found

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):

• neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030911028).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243156.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	NM_001243156.2	MANE Select	c.2341G>A	p.Val781Ile	missense	Exon 15 of 15	NP_001230085.2	Q15572-6
	TAF1C	NM_005679.4		c.2419G>A	p.Val807Ile	missense	Exon 14 of 14	NP_005670.4
	TAF1C	NM_139353.3		c.2137G>A	p.Val713Ile	missense	Exon 15 of 15	NP_647610.3	Q15572-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	ENST00000566732.6	TSL:2 MANE Select	c.2341G>A	p.Val781Ile	missense	Exon 15 of 15	ENSP00000455933.1	Q15572-6
	TAF1C	ENST00000341690.10	TSL:1	c.2137G>A	p.Val713Ile	missense	Exon 15 of 15	ENSP00000345305.6	Q15572-2
	TAF1C	ENST00000567759.5	TSL:2	c.2419G>A	p.Val807Ile	missense	Exon 14 of 14	ENSP00000455265.1	Q15572-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000616 AC: 15 AN: 243656 AF XY: 0.0000755

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000112

Gnomad NFE exome AF: 0.0000902

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000364 AC: 53 AN: 1455934 Hom.: 0 Cov.: 68 AF XY: 0.0000400 AC XY: 29 AN XY: 724224

African (AFR) AF: 0.000120 AC: 4 AN: 33448

American (AMR) AF: 0.0000448 AC: 2 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26026

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86146

European-Finnish (FIN) AF: 0.0000815 AC: 4 AN: 49062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1110952

Other (OTH) AF: 0.0000498 AC: 3 AN: 60274

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74314

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000663 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000742 AC: 9

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.016
DANN	Benign	0.81
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.38	N
REVEL	Benign	0.012
Sift	Benign	0.13	T
Sift4G	Benign	0.15	T
Polyphen		0.0030	B
Vest4		0.049
MVP		0.13
ClinPred		0.024	T
GERP RS		-3.8
Varity_R		0.019
gMVP		0.067
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs148942327; hg19: chr16-84212738; COSMIC: COSV58989221; COSMIC: COSV58989221;