Genetic Variant NM_025244.4:c.1509C>T (chr2-99035335-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_025244.4(TSGA10):c.1509C>T(p.Ser503Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,054 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 9 hom. )

Consequence

TSGA10
NM_025244.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 2-99035335-G-A is Benign according to our data. Variant chr2-99035335-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770650.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSGA10	NM_025244.4 link	c.1509C>T	p.Ser503Ser	synonymous_variant	Exon 17 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.1509C>T	p.Ser503Ser	synonymous_variant	Exon 17 of 21	1	NM_025244.4	ENSP00000377123.3		Q9BZW7-1

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00436

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00163

AC:

409

AN:

251264

Hom.:

AF XY:

0.00175

AC XY:

238

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00402

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00190

AC:

2781

AN:

1460998

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

1437

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000671

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.00369

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

152056

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

132

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00436

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00212

Hom.:

Bravo

AF:

0.00128

Asia WGS

AF:

0.000579

AC:

AN:

3466

EpiCase

AF:

0.00202

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TSGA10: BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -11

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