Genetic Variant TENT5D:p.Ile363Leu (chrX-80443626-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152630.5(TENT5D):c.1087A>C(p.Ile363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,096,814 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I363T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

TENT5D
NM_152630.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

Publications

0 publications found

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

new If you want to explore the variant's impact on the transcript NM_152630.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152630.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5D	NM_152630.5	MANE Select	c.1087A>C	p.Ile363Leu	missense	Exon 3 of 3	NP_689843.1	Q8NEK8
	TENT5D	NM_001170574.2		c.1087A>C	p.Ile363Leu	missense	Exon 5 of 5	NP_001164045.1	Q8NEK8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT5D	ENST00000308293.6	TSL:1 MANE Select	c.1087A>C	p.Ile363Leu	missense	Exon 3 of 3	ENSP00000308575.5	Q8NEK8
TENT5D	ENST00000538312.5	TSL:2	c.1087A>C	p.Ile363Leu	missense	Exon 5 of 5	ENSP00000443410.1	Q8NEK8
TENT5D	ENST00000927364.1		c.1087A>C	p.Ile363Leu	missense	Exon 4 of 4	ENSP00000597423.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1096814

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362582

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26361

American (AMR)

AF:

0.00

AC:

AN:

35078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19335

East Asian (EAS)

AF:

0.00

AC:

AN:

30174

South Asian (SAS)

AF:

0.00

AC:

AN:

54044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4130

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841245

Other (OTH)

AF:

0.00

AC:

AN:

45989

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.022

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.17

M_CAP

Benign

0.0024

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

1.7

PrimateAI

Benign

0.29

PROVEAN

Benign

0.18

REVEL

Benign

0.017

Sift

Benign

0.30

Sift4G

Benign

0.65

Varity_R

0.075

gMVP

0.38

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over