rs17037864

Variant names:

• chr4-158973239-G-A
• rs17037864
• NM_152543.3:c.137C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152543.3(SPMIP2):​c.137C>T​(p.Ala46Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,612,706 control chromosomes in the GnomAD database, including 16,471 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1205 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15266 hom.)
• Consequence: SPMIP2 NM_152543.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726
• Publications: 22 publications found

Genes affected

SPMIP2 (HGNC:26342): (sperm microtubule inner protein 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002533704).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152543.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPMIP2	NM_152543.3	MANE Select	c.137C>T	p.Ala46Val	missense	Exon 2 of 5	NP_689756.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPMIP2	ENST00000434826.3	TSL:2 MANE Select	c.137C>T	p.Ala46Val	missense	Exon 2 of 5	ENSP00000412215.2
	SPMIP2	ENST00000508011.1	TSL:3	n.232C>T		non_coding_transcript_exon	Exon 2 of 4
	SPMIP2	ENST00000505647.1	TSL:3	n.-108C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15349 AN: 151988 Hom.: 1206 Cov.: 32

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.0888

GnomAD2 exomes AF: 0.142 AC: 35371 AN: 248672 AF XY: 0.149

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.0764

Gnomad ASJ exome AF: 0.0421

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.154

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.134 AC: 195652 AN: 1460600 Hom.: 15266 Cov.: 33 AF XY: 0.137 AC XY: 99684 AN XY: 726584

African (AFR) AF: 0.0189 AC: 634 AN: 33476

American (AMR) AF: 0.0744 AC: 3324 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 1119 AN: 26122

East Asian (EAS) AF: 0.308 AC: 12208 AN: 39670

South Asian (SAS) AF: 0.253 AC: 21781 AN: 86174

European-Finnish (FIN) AF: 0.155 AC: 8257 AN: 53372

Middle Eastern (MID) AF: 0.0688 AC: 397 AN: 5768

European-Non Finnish (NFE) AF: 0.126 AC: 140221 AN: 1111004

Other (OTH) AF: 0.128 AC: 7711 AN: 60350

GnomAD4 genome AF: 0.101 AC: 15345 AN: 152106 Hom.: 1205 Cov.: 32 AF XY: 0.105 AC XY: 7802 AN XY: 74346

African (AFR) AF: 0.0236 AC: 981 AN: 41530

American (AMR) AF: 0.0648 AC: 990 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3464

East Asian (EAS) AF: 0.351 AC: 1818 AN: 5182

South Asian (SAS) AF: 0.258 AC: 1245 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1540 AN: 10548

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8326 AN: 67970

Other (OTH) AF: 0.0874 AC: 184 AN: 2106

Alfa AF: 0.114 Hom.: 4191

Bravo AF: 0.0912

TwinsUK AF: 0.137 AC: 507

ALSPAC AF: 0.127 AC: 490

ESP6500AA AF: 0.0287 AC: 105

ESP6500EA AF: 0.122 AC: 998

ExAC AF: 0.145 AC: 17485

Asia WGS AF: 0.243 AC: 846 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.13
DANN	Benign	0.77
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.49	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.58	N
PhyloP100		-0.73
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.013
Sift	Benign	0.23	T
Sift4G	Benign	0.32	T
Polyphen		0.0090	B
Vest4		0.022
MPC		0.0048
ClinPred		0.0043	T
GERP RS		-4.9
Varity_R		0.035
gMVP		0.23
Mutation Taster		=98/2	polymorphism (auto)

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: rs17037864; hg19: chr4-159894391; COSMIC: COSV71701273; COSMIC: COSV71701273;