Variant rs188396741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152630.5(TENT5D):c.391G>A(p.Val131Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,209,620 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000040 ( 0 hom. 11 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

TENT5D (HGNC:28399): (terminal nucleotidyltransferase 5D) Antibodies against the protein encoded by this gene were found only in plasma from cancer patients. While it may be a target for immunotherapy, the function of this gene is unknown. [provided by RefSeq, Dec 2009]

TENT5D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19083214).

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5D	NM_152630.5 link	c.391G>A	p.Val131Ile	missense_variant	Exon 3 of 3	ENST00000308293.6	NP_689843.1	Q8NEK8
TENT5D	NM_001170574.2 link	c.391G>A	p.Val131Ile	missense_variant	Exon 5 of 5		NP_001164045.1	Q8NEK8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT5D	ENST00000308293.6 link	c.391G>A	p.Val131Ile	missense_variant	Exon 3 of 3	1	NM_152630.5	ENSP00000308575.5		Q8NEK8
TENT5D	ENST00000538312.5 link	c.391G>A	p.Val131Ile	missense_variant	Exon 5 of 5	2		ENSP00000443410.1		Q8NEK8

Frequencies

GnomAD3 genomes

AF:

0.0000627

AC:

AN:

111715

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33991

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:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000657

AC:

AN:

182720

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

67488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000433

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1097853

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363407

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000132

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000439

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000626

AC:

AN:

111767

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34053

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.391G>A (p.V131I) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a G to A substitution at nucleotide position 391, causing the valine (V) at amino acid position 131 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

T;T

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.

M_CAP

Benign

0.0070

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.85

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.26

Sift

Benign

0.15

T;T

Sift4G

Benign

0.093

T;T

Polyphen

1.0

D;D

Vest4

0.41

MVP

0.51

MPC

0.99

ClinPred

0.35

GERP RS

4.4

Varity_R

0.25

gMVP

0.40

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