dbSNP rs2085592818: TSGA10:p.Val389Asp (chr2-99068940-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025244.4(TSGA10):c.1166T>A(p.Val389Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,321,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

TSGA10
NM_025244.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

TSGA10 (HGNC:14927): (testis specific 10) Predicted to enable structural molecule activity. Predicted to be involved in spermatogenesis. Predicted to act upstream of or within cell projection assembly. Predicted to be located in neuron projection; sperm fibrous sheath; and sperm principal piece. Implicated in spermatogenic failure 26. [provided by Alliance of Genome Resources, Apr 2022]

TSGA10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30697364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSGA10	NM_025244.4 link	c.1166T>A	p.Val389Asp	missense_variant	Exon 15 of 21	ENST00000393483.8	NP_079520.1	Q9BZW7-1A0A218MIY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSGA10	ENST00000393483.8 link	c.1166T>A	p.Val389Asp	missense_variant	Exon 15 of 21	1	NM_025244.4	ENSP00000377123.3		Q9BZW7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.56e-7

AC:

AN:

1321982

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

653556

show subpopulations

African (AFR)

AF:

0.0000372

AC:

AN:

26888

American (AMR)

AF:

0.00

AC:

AN:

23362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21766

East Asian (EAS)

AF:

0.00

AC:

AN:

32800

South Asian (SAS)

AF:

0.00

AC:

AN:

58314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49916

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1049570

Other (OTH)

AF:

0.00

AC:

AN:

54062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1166T>A (p.V389D) alteration is located in exon 15 (coding exon 10) of the TSGA10 gene. This alteration results from a T to A substitution at nucleotide position 1166, causing the valine (V) at amino acid position 389 to be replaced by an aspartic acid (D). 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

0.77

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.36

T;T;T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.43

LIST_S2

Uncertain

0.90

.;.;D;D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.31

T;T;T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.5

L;L;L;.;.

PhyloP100

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.4

D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Benign

0.58

T;T;T;.;.

Polyphen

0.078

B;B;B;.;.

Vest4

0.85

MutPred

0.21

Loss of MoRF binding (P = 0.0234);Loss of MoRF binding (P = 0.0234);Loss of MoRF binding (P = 0.0234);Loss of MoRF binding (P = 0.0234);Loss of MoRF binding (P = 0.0234);

MVP

0.96

MPC

0.29

ClinPred

0.81

GERP RS

3.7

Varity_R

0.73

gMVP

0.77

Mutation Taster

=86/14

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

Publications

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rs2085592818

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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