Variant chrX-80442562-A-G 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.23A>G(p.Asn8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000499 in 1,203,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000041 ( 0 hom. 19 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.301

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=0.068810165).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENT5D	NM_152630.5 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	3/3	ENST00000308293.6
TENT5D	NM_001170574.2 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENT5D	ENST00000308293.6 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	3/3	1	NM_152630.5	P1
TENT5D	ENST00000538312.5 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	5/5	2		P1

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

112357

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

34589

show subpopulations

Gnomad AFR

AF:

0.000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000189

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000524

AC:

AN:

171795

Hom.:

AF XY:

0.0000519

AC XY:

AN XY:

57791

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000758

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000653

Gnomad NFE exome

AF:

0.0000786

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000413

AC:

AN:

1090660

Hom.:

Cov.:

AF XY:

0.0000531

AC XY:

AN XY:

357576

show subpopulations

Gnomad4 AFR exome

AF:

0.0000762

Gnomad4 AMR exome

AF:

0.000115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000249

Gnomad4 NFE exome

AF:

0.0000394

Gnomad4 OTH exome

AF:

0.0000875

GnomAD4 genome

AF:

0.000133

AC:

AN:

112410

Hom.:

Cov.:

AF XY:

0.0000866

AC XY:

AN XY:

34652

show subpopulations

Gnomad4 AFR

AF:

0.000322

Gnomad4 AMR

AF:

0.000189

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000825

AC:

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

Jan 02, 2024

The c.23A>G (p.N8S) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a A to G substitution at nucleotide position 23, causing the asparagine (N) at amino acid position 8 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.020

DANN

Benign

0.28

DEOGEN2

Benign

0.019

T;T

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.18

T;.

M_CAP

Benign

0.0045

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.60

N;N

REVEL

Benign

0.0070

Sift

Benign

0.79

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0030

B;B

Vest4

0.066

MVP

0.068

MPC

0.28

ClinPred

0.022

GERP RS

-2.5

Varity_R

0.024

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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