12-49496980-A-T

Variant names:

• chr12-49496980-A-T
• rs764764954
• NM_023071.4:c.674A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023071.4(SPATS2):​c.674A>T​(p.Asp225Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000694 in 1,584,514 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

Genes affected

SPATS2 (HGNC:18650): (spermatogenesis associated serine rich 2) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATS2	NM_023071.4	c.674A>T	p.Asp225Val	missense_variant	Exon 8 of 14	ENST00000552918.6	NP_075559.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATS2	ENST00000552918.6	c.674A>T	p.Asp225Val	missense_variant	Exon 8 of 14	2	NM_023071.4	ENSP00000447947.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00000452 AC: 1 AN: 221358 Hom.: 0 AF XY: 0.00000832 AC XY: 1 AN XY: 120182

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000638

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000628 AC: 9 AN: 1432168 Hom.: 0 Cov.: 31 AF XY: 0.00000562 AC XY: 4 AN XY: 711310

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000800

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000546

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2 AN XY: 74502

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	.;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.43	T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.5	L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.96	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.17	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.52
MutPred		0.51		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.17
MPC		0.82
ClinPred		0.49	T
GERP RS		3.1
Varity_R		0.13
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs764764954; hg19: chr12-49890763;