chr2-99068884-A-C

Variant names:

• chr2-99068884-A-C
• rs145023979
• NM_025244.4:c.1218+4T>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_025244.4(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 NM_025244.4 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

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TSGA10	NM_025244.4	c.1218+4T>G		splice_region_variant, intron_variant	Intron 15 of 20	ENST00000393483.8	NP_079520.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSGA10	ENST00000393483.8	c.1218+4T>G		splice_region_variant, intron_variant	Intron 15 of 20	1	NM_025244.4	ENSP00000377123.3

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 784 AN: 152104 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00522 AC: 833 AN: 159488 AF XY: 0.00548

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 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.: 32 Cov.: 18 AF XY: 0.00586 AC XY: 3557 AN XY: 606726

Gnomad4 AFR exome AF: 0.000886 AC: 22 AN: 24830

Gnomad4 AMR exome AF: 0.00597 AC: 121 AN: 20284

Gnomad4 ASJ exome AF: 0.00341 AC: 68 AN: 19964

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 31862

Gnomad4 SAS exome AF: 0.00258 AC: 131 AN: 50822

Gnomad4 FIN exome AF: 0.00658 AC: 314 AN: 47728

Gnomad4 NFE exome AF: 0.00641 AC: 6251 AN: 975722

Gnomad4 Remaining exome AF: 0.00652 AC: 328 AN: 50338

GnomAD4 genome AF: 0.00516 AC: 785 AN: 152222 Hom.: 1 Cov.: 32 AF XY: 0.00525 AC XY: 391 AN XY: 74422

Gnomad4 AFR AF: 0.00164 AC: 0.00163674 AN: 0.00163674

Gnomad4 AMR AF: 0.00720 AC: 0.00720178 AN: 0.00720178

Gnomad4 ASJ AF: 0.00346 AC: 0.00346021 AN: 0.00346021

Gnomad4 EAS AF: 0.000193 AC: 0.000193125 AN: 0.000193125

Gnomad4 SAS AF: 0.00228 AC: 0.00227932 AN: 0.00227932

Gnomad4 FIN AF: 0.00765 AC: 0.00765017 AN: 0.00765017

Gnomad4 NFE AF: 0.00707 AC: 0.00707124 AN: 0.00707124

Gnomad4 OTH AF: 0.00946 AC: 0.00946074 AN: 0.00946074

Alfa AF: 0.00561 Hom.: 5

Bravo AF: 0.00507

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TSGA10: BP4, BS2 -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

TSGA10-related disorder Benign:1

Mar 28, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs145023979; hg19: chr2-99685347;