rs2230129

Variant names:

• chr16-84179828-A-C
• NM_001243156.2:c.1645T>G

Your query was ambiguous. Multiple possible variants found:

• chr16-84179828-A-C
• chr16-84179828-A-G
• chr16-84179828-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001243156.2(TAF1C):​c.1645T>G​(p.Leu549Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAF1C NM_001243156.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04735595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1C	NM_001243156.2	c.1645T>G	p.Leu549Val	missense_variant	Exon 15 of 15	ENST00000566732.6	NP_001230085.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1C	ENST00000566732.6	c.1645T>G	p.Leu549Val	missense_variant	Exon 15 of 15	2	NM_001243156.2	ENSP00000455933.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454914 Hom.: 0 Cov.: 84 AF XY: 0.00000138 AC XY: 1 AN XY: 722838

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.57
DANN	Benign	0.88
DEOGEN2	Benign	0.0056	.;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.34	T;T;T;T;.
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.047	T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	.;.;N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.76	.;N;N;N;N
REVEL	Benign	0.011
Sift	Benign	0.17	.;T;T;T;T
Sift4G	Benign	0.68	T;T;T;T;T
Polyphen		0.017	.;B;B;B;.
Vest4		0.041
MutPred		0.17		.;.;Loss of helix (P = 0.079);.;.;
MVP		0.16
ClinPred		0.041	T
GERP RS		1.2
Varity_R		0.052
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-84213434;