NM_025244.4:c.1295G>A

Variant names:

• chr2-99065048-C-T
• rs751796811
• NM_025244.4:c.1295G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025244.4(TSGA10):​c.1295G>A​(p.Arg432His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TSGA10 NM_025244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355
• Publications: 3 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.032621592).

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.1295G>A	p.Arg432His	missense	Exon 16 of 21	NP_079520.1	A0A218MIY9
	TSGA10	NM_001349012.1		c.1295G>A	p.Arg432His	missense	Exon 14 of 19	NP_001335941.1	A0A218MIY9
	TSGA10	NM_182911.4		c.1295G>A	p.Arg432His	missense	Exon 15 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.1295G>A	p.Arg432His	missense	Exon 16 of 21	ENSP00000377123.3	Q9BZW7-1
	TSGA10	ENST00000355053.8	TSL:1	c.1295G>A	p.Arg432His	missense	Exon 15 of 20	ENSP00000347161.4	Q9BZW7-1
	TSGA10	ENST00000410001.5	TSL:1	c.1295G>A	p.Arg432His	missense	Exon 14 of 19	ENSP00000386956.1	Q9BZW7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251264 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461644 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727110

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.0000671 AC: 3 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.16
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.52	N
PhyloP100		0.35
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.054
Sift	Benign	0.98	T
Sift4G	Benign	0.63	T
Polyphen		0.0030	B
Vest4		0.065
MutPred		0.17		Loss of MoRF binding (P = 0.0645)
MVP		0.093
MPC		0.15
ClinPred		0.10	T
GERP RS		3.5
Varity_R		0.025
gMVP		0.097
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs751796811; hg19: chr2-99681511; COSMIC: COSV61825697; COSMIC: COSV61825697;