Variant 3-56624574-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365635.2(TASOR):c.4388T>G(p.Met1463Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TASOR
NM_001365635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.54

Variant links:

Genes affected

TASOR (HGNC:30314): (transcription activation suppressor) Enables chromatin binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; protein localization to heterochromatin; and regulation of gene expression. Located in heterochromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TASOR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TASOR	NM_001365635.2 link	c.4388T>G	p.Met1463Arg	missense_variant	23/24	ENST00000683822.1	NP_001352564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TASOR	ENST00000683822.1 link	c.4388T>G	p.Met1463Arg	missense_variant	23/24		NM_001365635.2	ENSP00000508241.1		Q9UK61-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251252

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727138

show subpopulations

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:

0.0000306

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.4388T>G (p.M1463R) alteration is located in exon 23 (coding exon 23) of the FAM208A gene. This alteration results from a T to G substitution at nucleotide position 4388, causing the methionine (M) at amino acid position 1463 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

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.23

.;.;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.72

D;D;D;D

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-4.2

D;D;D;.

REVEL

Uncertain

0.38

Sift

Benign

0.035

D;D;.;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.98

D;P;P;.

Vest4

0.92

MutPred

0.51

.;Gain of catalytic residue at M1463 (P = 0.0038);.;.;

MVP

0.26

MPC

1.1

ClinPred

0.42

GERP RS

5.4

gMVP

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over