Variant 2-99068884-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000393483.8(TSGA10):c.1218+4T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00585 in 1,378,796 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0059 ( 32 hom. )

Consequence

TSGA10
ENST00000393483.8 splice_region, intron

Scores

Splicing: ADA: 0.0006543

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.137

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:

TSGA10 (HGNC:):

TSGA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-99068884-A-C is Benign according to our data. Variant chr2-99068884-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 773485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TSGA10	NM_025244.4 linkuse as main transcript	c.1218+4T>G		splice_region_variant, intron_variant		ENST00000393483.8	NP_079520.1	Q9BZW7-1A0A218MIY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TSGA10	ENST00000393483.8 linkuse as main transcript	c.1218+4T>G		splice_region_variant, intron_variant		1	NM_025244.4	ENSP00000377123.3		Q9BZW7-1

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

784

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00721

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00765

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00707

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.00522

AC:

833

AN:

159488

Hom.:

AF XY:

0.00548

AC XY:

488

AN XY:

88992

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.00453

Gnomad ASJ exome

AF:

0.00277

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00271

Gnomad FIN exome

AF:

0.00606

Gnomad NFE exome

AF:

0.00693

Gnomad OTH exome

AF:

0.00732

GnomAD4 exome

AF:

0.00594

AC:

7287

AN:

1226574

Hom.:

Cov.:

AF XY:

0.00586

AC XY:

3557

AN XY:

606726

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.00597

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00258

Gnomad4 FIN exome

AF:

0.00658

Gnomad4 NFE exome

AF:

0.00641

Gnomad4 OTH exome

AF:

0.00652

GnomAD4 genome

AF:

0.00516

AC:

785

AN:

152222

Hom.:

Cov.:

AF XY:

0.00525

AC XY:

391

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00720

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00765

Gnomad4 NFE

AF:

0.00707

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.00561

Hom.:

Bravo

AF:

0.00507

Asia WGS

AF:

0.00145

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	TSGA10: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

TSGA10-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.3

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00065

dbscSNV1_RF

Benign

0.17

SpliceAI score (max)

0.12

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