9-32630728-T-G

Variant names:

• chr9-32630728-T-G
• rs781319177
• NM_153809.2:c.4852A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153809.2(TAF1L):​c.4852A>C​(p.Ile1618Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I1618V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1L NM_153809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• Publications: 0 publications found

Genes affected

TAF1L (HGNC:18056): (TATA-box binding protein associated factor 1 like) This locus is intronless, and apparently arose in the primate lineage from retrotransposition of the transcript from the multi-exon TAF1 locus on the X chromosome. The gene is expressed in male germ cells, and the product has been shown to function interchangeably with the TAF1 product. [provided by RefSeq, Aug 2015]

ENSG00000295509 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07721907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1L	NM_153809.2	c.4852A>C	p.Ile1618Leu	missense_variant	Exon 1 of 1	ENST00000242310.4	NP_722516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1L	ENST00000242310.4	c.4852A>C	p.Ile1618Leu	missense_variant	Exon 1 of 1	6	NM_153809.2	ENSP00000418379.1
ENSG00000295509	ENST00000730514.1	n.252-21723A>C		intron_variant	Intron 2 of 3
ENSG00000295509	ENST00000730515.1	n.319-21723A>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000570 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.57
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.047	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.38
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.023
Sift	Benign	0.43	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.42		Gain of catalytic residue at I1618 (P = 0.3313);
MVP		0.26
MPC		0.13
ClinPred		0.18	T
GERP RS		-0.76
Varity_R		0.32
gMVP		0.38
Mutation Taster		=85/15	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: rs781319177; hg19: chr9-32630726;