rs368760386

Variant names:

• chr2-99035334-C-A
• rs368760386
• NM_025244.4:c.1510G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-99035334-C-A
• chr2-99035334-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_025244.4(TSGA10):​c.1510G>T​(p.Ala504Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A504T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TSGA10 NM_025244.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.841
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.1510G>T	p.Ala504Ser	missense	Exon 17 of 21	NP_079520.1	A0A218MIY9
	TSGA10	NM_001349012.1		c.1510G>T	p.Ala504Ser	missense	Exon 15 of 19	NP_001335941.1	A0A218MIY9
	TSGA10	NM_182911.4		c.1510G>T	p.Ala504Ser	missense	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.1510G>T	p.Ala504Ser	missense	Exon 17 of 21	ENSP00000377123.3	Q9BZW7-1
	TSGA10	ENST00000355053.8	TSL:1	c.1510G>T	p.Ala504Ser	missense	Exon 16 of 20	ENSP00000347161.4	Q9BZW7-1
	TSGA10	ENST00000410001.5	TSL:1	c.1510G>T	p.Ala504Ser	missense	Exon 15 of 19	ENSP00000386956.1	Q9BZW7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.84
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.13	T
Sift4G	Benign	0.80	T
Polyphen		0.99	D
Vest4		0.46
MutPred		0.20		Gain of phosphorylation at A504 (P = 0.0322)
MVP		0.21
MPC		0.35
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.080
gMVP		0.093
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.55		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.55		Position offset: -10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs368760386; hg19: chr2-99651797;