Variant X-80442870-T-C 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.331T>C(p.Phe111Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,209,189 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 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 0.000081 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 61 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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=0.16051328).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT5D	NM_152630.5 link	c.331T>C	p.Phe111Leu	missense_variant	Exon 3 of 3	ENST00000308293.6	NP_689843.1	Q8NEK8
TENT5D	NM_001170574.2 link	c.331T>C	p.Phe111Leu	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.331T>C	p.Phe111Leu	missense_variant	Exon 3 of 3	1	NM_152630.5	ENSP00000308575.5		Q8NEK8
TENT5D	ENST00000538312.5 link	c.331T>C	p.Phe111Leu	missense_variant	Exon 5 of 5	2		ENSP00000443410.1		Q8NEK8

Frequencies

GnomAD3 genomes

AF:

0.0000808

AC:

AN:

111420

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33698

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:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000822

AC:

AN:

182568

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

67398

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:

0.000125

Gnomad NFE exome

AF:

0.000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000135

AC:

148

AN:

1097769

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

AN XY:

363315

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

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:

0.000222

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000808

AC:

AN:

111420

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33698

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:

0.000165

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000195

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.331T>C (p.F111L) alteration is located in exon 5 (coding exon 1) of the FAM46D gene. This alteration results from a T to C substitution at nucleotide position 331, causing the phenylalanine (F) at amino acid position 111 to be replaced by a leucine (L). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.054

T;T

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;.

M_CAP

Benign

0.0047

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.13

Sift

Benign

0.47

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.071

B;B

Vest4

0.28

MutPred

0.56

Loss of methylation at K114 (P = 0.0916);Loss of methylation at K114 (P = 0.0916);

MVP

0.27

MPC

0.46

ClinPred

0.11

GERP RS

4.3

Varity_R

0.40

gMVP

0.41

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