X-80442907-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152630.5(TENT5D):c.368C>T(p.Pro123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,209,314 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P123A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000046 ( 0 hom. 24 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.825

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062651336).

BP6

Variant X-80442907-C-T is Benign according to our data. Variant chrX-80442907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3176091.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENT5D	NM_152630.5 linkuse as main transcript	c.368C>T	p.Pro123Leu	missense_variant	3/3	ENST00000308293.6
TENT5D	NM_001170574.2 linkuse as main transcript	c.368C>T	p.Pro123Leu	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENT5D	ENST00000308293.6 linkuse as main transcript	c.368C>T	p.Pro123Leu	missense_variant	3/3	1	NM_152630.5	P1
TENT5D	ENST00000538312.5 linkuse as main transcript	c.368C>T	p.Pro123Leu	missense_variant	5/5	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111455

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33731

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

182686

Hom.:

AF XY:

0.0000889

AC XY:

AN XY:

67458

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:

0.00

Gnomad NFE exome

AF:

0.0000861

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1097859

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

363409

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.00000897

AC:

AN:

111455

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33731

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:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.96

Cadd

Benign

0.43

Dann

Benign

0.32

DEOGEN2

Benign

0.072

T;T

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.65

T;.

M_CAP

Benign

0.0011

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.067

Sift

Benign

0.38

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0

B;B

Vest4

0.036

MutPred

0.53

Loss of disorder (P = 0.0324);Loss of disorder (P = 0.0324);

MVP

0.043

MPC

0.35

ClinPred

0.033

GERP RS

-2.9

Varity_R

0.058

gMVP

0.15

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