rs72813051

Variant names:

• chr2-99035335-G-A
• rs72813051
• NM_025244.4:c.1509C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 26

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 3770650.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025244.4. 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
	TSGA10	NM_025244.4	MANE Select	c.1509C>T	p.Ser503Ser	synonymous	Exon 17 of 21	NP_079520.1	A0A218MIY9
	TSGA10	NM_001349012.1		c.1509C>T	p.Ser503Ser	synonymous	Exon 15 of 19	NP_001335941.1	A0A218MIY9
	TSGA10	NM_182911.4		c.1509C>T	p.Ser503Ser	synonymous	Exon 16 of 20	NP_878915.2	A0A218MIY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSGA10	ENST00000393483.8	TSL:1 MANE Select	c.1509C>T	p.Ser503Ser	synonymous	Exon 17 of 21	ENSP00000377123.3	Q9BZW7-1
	TSGA10	ENST00000355053.8	TSL:1	c.1509C>T	p.Ser503Ser	synonymous	Exon 16 of 20	ENSP00000347161.4	Q9BZW7-1
	TSGA10	ENST00000410001.5	TSL:1	c.1509C>T	p.Ser503Ser	synonymous	Exon 15 of 19	ENSP00000386956.1	Q9BZW7-1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 151940 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.00163 AC: 409 AN: 251264 AF XY: 0.00175

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 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.: 9 Cov.: 31 AF XY: 0.00198 AC XY: 1437 AN XY: 726790

African (AFR) AF: 0.000120 AC: 4 AN: 33456

American (AMR) AF: 0.000671 AC: 30 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000575 AC: 15 AN: 26108

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39580

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86160

European-Finnish (FIN) AF: 0.00369 AC: 197 AN: 53410

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5760

European-Non Finnish (NFE) AF: 0.00215 AC: 2393 AN: 1111454

Other (OTH) AF: 0.00151 AC: 91 AN: 60356

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152056 Hom.: 0 Cov.: 32 AF XY: 0.00178 AC XY: 132 AN XY: 74330

African (AFR) AF: 0.000169 AC: 7 AN: 41502

American (AMR) AF: 0.000458 AC: 7 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00436 AC: 46 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 67944

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00197 Hom.: 1

Bravo AF: 0.00128

Asia WGS AF: 0.000579 AC: 2 AN: 3466

EpiCase AF: 0.00202

EpiControl AF: 0.00130

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.61
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs72813051; hg19: chr2-99651798; COSMIC: COSV61823768;