chr12-49496911-C-G

Variant names:

• chr12-49496911-C-G
• rs191343457
• NM_023071.4:c.605C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_023071.4(SPATS2):​c.605C>G​(p.Pro202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,613,288 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (1 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0066134334).

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.605C>G	p.Pro202Arg	missense	Exon 8 of 14	NP_075559.2	Q86XZ4
	SPATS2	NM_001293285.2		c.605C>G	p.Pro202Arg	missense	Exon 9 of 15	NP_001280214.1	Q86XZ4
	SPATS2	NM_001293286.2		c.605C>G	p.Pro202Arg	missense	Exon 7 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.605C>G	p.Pro202Arg	missense	Exon 8 of 14	ENSP00000447947.2	Q86XZ4
	SPATS2	ENST00000321898.10	TSL:1	c.605C>G	p.Pro202Arg	missense	Exon 7 of 13	ENSP00000326841.6	Q86XZ4
	SPATS2	ENST00000553127.5	TSL:1	c.605C>G	p.Pro202Arg	missense	Exon 9 of 15	ENSP00000448228.1	Q86XZ4

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152140 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: 0.00135

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: 0.000132 AC: 33 AN: 250354 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00175

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461030 Hom.: 1 Cov.: 31 AF XY: 0.0000564 AC XY: 41 AN XY: 726824

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00161 AC: 64 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111726

Other (OTH) AF: 0.0000497 AC: 3 AN: 60372

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000176 Hom.: 0

Bravo AF: 0.0000907

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.088
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.44
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.026
Sift	Benign	0.085	T
Sift4G	Benign	0.065	T
Polyphen		0.0010	B
Vest4		0.17
MVP		0.043
MPC		0.22
ClinPred		0.018	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.045
gMVP		0.19
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs191343457; hg19: chr12-49890694;