12-49484638-A-G

Variant names:

• chr12-49484638-A-G
• rs749492187
• NM_023071.4:c.74A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_023071.4(SPATS2):​c.74A>G​(p.Gln25Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.46
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15419471).

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.74A>G	p.Gln25Arg	missense	Exon 4 of 14	NP_075559.2	Q86XZ4
	SPATS2	NM_001293285.2		c.74A>G	p.Gln25Arg	missense	Exon 5 of 15	NP_001280214.1	Q86XZ4
	SPATS2	NM_001293286.2		c.74A>G	p.Gln25Arg	missense	Exon 3 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.74A>G	p.Gln25Arg	missense	Exon 4 of 14	ENSP00000447947.2	Q86XZ4
	SPATS2	ENST00000321898.10	TSL:1	c.74A>G	p.Gln25Arg	missense	Exon 3 of 13	ENSP00000326841.6	Q86XZ4
	SPATS2	ENST00000553127.5	TSL:1	c.74A>G	p.Gln25Arg	missense	Exon 5 of 15	ENSP00000448228.1	Q86XZ4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152190 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251384 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461728 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111914

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152308 Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000480 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions

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	0.20
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.074	T
Sift4G	Benign	0.083	T
Polyphen		0.99	D
Vest4		0.42
MutPred		0.26		Gain of methylation at Q25 (P = 0.0432)
MVP		0.23
MPC		0.77
ClinPred		0.45	T
GERP RS		5.4
Varity_R		0.30
gMVP		0.70
Mutation Taster		=78/22	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: rs749492187; hg19: chr12-49878421;