12-49494763-C-G

Variant names:

• chr12-49494763-C-G
• rs146383919
• NM_023071.4:c.287C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_023071.4(SPATS2):​c.287C>G​(p.Pro96Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000704 in 1,421,338 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P96L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023071.4. 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
	SPATS2	NM_023071.4	MANE Select	c.287C>G	p.Pro96Arg	missense	Exon 7 of 14	NP_075559.2	Q86XZ4
	SPATS2	NM_001293285.2		c.287C>G	p.Pro96Arg	missense	Exon 8 of 15	NP_001280214.1	Q86XZ4
	SPATS2	NM_001293286.2		c.287C>G	p.Pro96Arg	missense	Exon 6 of 13	NP_001280215.1	Q86XZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATS2	ENST00000552918.6	TSL:2 MANE Select	c.287C>G	p.Pro96Arg	missense	Exon 7 of 14	ENSP00000447947.2	Q86XZ4
	SPATS2	ENST00000321898.10	TSL:1	c.287C>G	p.Pro96Arg	missense	Exon 6 of 13	ENSP00000326841.6	Q86XZ4
	SPATS2	ENST00000553127.5	TSL:1	c.287C>G	p.Pro96Arg	missense	Exon 8 of 15	ENSP00000448228.1	Q86XZ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1421338 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704370

African (AFR) AF: 0.00 AC: 0 AN: 31732

American (AMR) AF: 0.00 AC: 0 AN: 35786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24812

East Asian (EAS) AF: 0.00 AC: 0 AN: 38336

South Asian (SAS) AF: 0.00 AC: 0 AN: 79476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1094562

Other (OTH) AF: 0.00 AC: 0 AN: 58822

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.39
MutPred		0.41		Loss of glycosylation at P96 (P = 0.0085)
MVP		0.10
MPC		0.77
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.23
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs146383919; hg19: chr12-49888546;