Variant chr3-56627133-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001365635.2(TASOR):c.4043A>T(p.Asn1348Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,601,962 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 2 hom. )

Consequence

TASOR
NM_001365635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.138

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TASOR	NM_001365635.2 linkuse as main transcript	c.4043A>T	p.Asn1348Ile	missense_variant	21/24	ENST00000683822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TASOR	ENST00000683822.1 linkuse as main transcript	c.4043A>T	p.Asn1348Ile	missense_variant	21/24		NM_001365635.2	A2	Q9UK61-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

247768

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134132

show subpopulations

Gnomad AFR exome

AF:

0.000686

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000911

AC:

132

AN:

1449602

Hom.:

Cov.:

AF XY:

0.0000928

AC XY:

AN XY:

721932

show subpopulations

Gnomad4 AFR exome

AF:

0.000667

Gnomad4 AMR exome

AF:

0.0000685

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.000328

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000553

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000223

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000547

EpiControl

AF:

0.0000593

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

May 27, 2022

The c.4043A>T (p.N1348I) alteration is located in exon 21 (coding exon 21) of the FAM208A gene. This alteration results from a A to T substitution at nucleotide position 4043, causing the asparagine (N) at amino acid position 1348 to be replaced by an isoleucine (I). 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

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.057

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.68

T;T;T;T

M_CAP

Benign

0.0093

MetaRNN

Benign

0.017

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.9

D;N;N;.

REVEL

Benign

0.024

Sift

Benign

0.26

T;T;.;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.22

MVP

0.093

MPC

0.32

ClinPred

0.022

GERP RS

-4.6

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -20

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