Variant rs749617118 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152630.5(TENT5D):c.367C>G(p.Pro123Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,097,855 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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: not found (cov: 23)

Exomes 𝑓: 0.000015 ( 0 hom. 8 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.697

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.038685292).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5D	NM_152630.5 link	c.367C>G	p.Pro123Ala	missense_variant	Exon 3 of 3	ENST00000308293.6	NP_689843.1	Q8NEK8
TENT5D	NM_001170574.2 link	c.367C>G	p.Pro123Ala	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.367C>G	p.Pro123Ala	missense_variant	Exon 3 of 3	1	NM_152630.5	ENSP00000308575.5		Q8NEK8
TENT5D	ENST00000538312.5 link	c.367C>G	p.Pro123Ala	missense_variant	Exon 5 of 5	2		ENSP00000443410.1		Q8NEK8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

182689

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

67459

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:

0.000419

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1097855

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

363405

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:

0.000240

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

Cov.:

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

Nov 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.367C>G (p.P123A) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a C to G substitution at nucleotide position 367, causing the proline (P) at amino acid position 123 to be replaced by an alanine (A). 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

0.059

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.033

DANN

Benign

0.28

DEOGEN2

Benign

0.025

T;T

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.65

T;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.092

Sift

Benign

0.40

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

B;B

Vest4

0.023

MutPred

0.52

Loss of methylation at K118 (P = 0.052);Loss of methylation at K118 (P = 0.052);

MVP

0.043

MPC

0.33

ClinPred

0.023

GERP RS

1.3

Varity_R

0.037

gMVP

0.064

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