rs61733031

Variant names:

• chr12-49484628-G-A
• rs61733031
• NM_023071.4:c.64G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-49484628-G-A
• chr12-49484628-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_023071.4(SPATS2):​c.64G>A​(p.Val22Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,613,880 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (56 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (50 hom.)
• Consequence: SPATS2 NM_023071.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 8.75
• Publications: 6 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003194213).
• BP6: Variant 12-49484628-G-A is Benign according to our data. Variant chr12-49484628-G-A is described in ClinVar as Benign. ClinVar VariationId is 787394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

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.64G>A	p.Val22Ile	missense	Exon 4 of 14	NP_075559.2	Q86XZ4
	SPATS2	NM_001293285.2		c.64G>A	p.Val22Ile	missense	Exon 5 of 15	NP_001280214.1	Q86XZ4
	SPATS2	NM_001293286.2		c.64G>A	p.Val22Ile	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.64G>A	p.Val22Ile	missense	Exon 4 of 14	ENSP00000447947.2	Q86XZ4
	SPATS2	ENST00000321898.10	TSL:1	c.64G>A	p.Val22Ile	missense	Exon 3 of 13	ENSP00000326841.6	Q86XZ4
	SPATS2	ENST00000553127.5	TSL:1	c.64G>A	p.Val22Ile	missense	Exon 5 of 15	ENSP00000448228.1	Q86XZ4

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2263 AN: 152054 Hom.: 56 Cov.: 31

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00424 AC: 1067 AN: 251374 AF XY: 0.00311

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00625

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00168 AC: 2461 AN: 1461708 Hom.: 50 Cov.: 30 AF XY: 0.00147 AC XY: 1069 AN XY: 727150

African (AFR) AF: 0.0532 AC: 1780 AN: 33466

American (AMR) AF: 0.00163 AC: 73 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00574 AC: 150 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39662

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86246

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53414

Middle Eastern (MID) AF: 0.00589 AC: 34 AN: 5768

European-Non Finnish (NFE) AF: 0.000146 AC: 162 AN: 1111914

Other (OTH) AF: 0.00368 AC: 222 AN: 60390

GnomAD4 genome AF: 0.0149 AC: 2268 AN: 152172 Hom.: 56 Cov.: 31 AF XY: 0.0144 AC XY: 1071 AN XY: 74390

African (AFR) AF: 0.0515 AC: 2137 AN: 41496

American (AMR) AF: 0.00431 AC: 66 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68008

Other (OTH) AF: 0.0104 AC: 22 AN: 2110

Alfa AF: 0.00509 Hom.: 34

Bravo AF: 0.0169

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0499 AC: 220

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00518 AC: 629

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		8.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.13
Sift	Benign	0.071	T
Sift4G	Benign	0.091	T
Polyphen		1.0	D
Vest4		0.37
MVP		0.38
MPC		0.67
ClinPred		0.045	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.24
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs61733031; hg19: chr12-49878411; COSMIC: COSV58916749; COSMIC: COSV58916749;