Genetic Variant TAF1L:p.Gly1659Arg (chr9-32630605-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_153809.2(TAF1L):c.4975G>C(p.Gly1659Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TAF1L
NM_153809.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83

Publications

0 publications found

Variant links:

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]

TAF1L links:

ENSG00000295509 (HGNC:):

ENSG00000295509 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.12626529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1L	NM_153809.2 link	c.4975G>C	p.Gly1659Arg	missense_variant	Exon 1 of 1	ENST00000242310.4	NP_722516.1	Q8IZX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAF1L	ENST00000242310.4 link	c.4975G>C	p.Gly1659Arg	missense_variant	Exon 1 of 1	6	NM_153809.2	ENSP00000418379.1	Q8IZX4
ENSG00000295509	ENST00000730514.1 link	n.252-21600G>C		intron_variant	Intron 2 of 3
ENSG00000295509	ENST00000730515.1 link	n.319-21600G>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000756

AC:

AN:

251484

AF XY:

0.0000441

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000378

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 08, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.4975G>C (p.G1659R) alteration is located in exon 1 (coding exon 1) of the TAF1L gene. This alteration results from a G to C substitution at nucleotide position 4975, causing the glycine (G) at amino acid position 1659 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

Eigen

Benign

0.066

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.0047

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

4.8

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.14

Sift

Uncertain

0.0080

Sift4G

Benign

0.091

Polyphen

1.0

Vest4

0.25

MutPred

0.34

Gain of solvent accessibility (P = 0.0097);

MVP

0.48

MPC

0.66

ClinPred

0.39

GERP RS

0.48

Varity_R

0.32

gMVP

0.46

Mutation Taster

=71/29

polymorphism

(source)

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

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9-32630605-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over