rs17037864

Positions:

• chr4-158973239-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152543.3(C4orf45):​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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (1205 hom., cov: 32)
  • Exomes 𝑓: 0.13 (15266 hom.)
• Consequence: C4orf45 NM_152543.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.726

Genes affected

C4orf45 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4orf45	NM_152543.3	c.137C>T	p.Ala46Val	missense_variant	2/5	ENST00000434826.3	NP_689756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP2	ENST00000434826.3	c.137C>T	p.Ala46Val	missense_variant	2/5	2	NM_152543.3	ENSP00000412215	P1
SPMIP2	ENST00000508011.1	n.232C>T		non_coding_transcript_exon_variant	2/4	3

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

GnomAD3 exomes AF: 0.142 AC: 35371 AN: 248672 Hom.: 3400 AF XY: 0.149 AC XY: 20142 AN XY: 134892

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 SAS exome AF: 0.252

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

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.0744

Gnomad4 ASJ exome AF: 0.0428

Gnomad4 EAS exome AF: 0.308

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.128

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

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.0648

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0874

Alfa AF: 0.117 Hom.: 3182

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 v4.3

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
MutationTaster	Benign	1.0	P
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

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

Publications

LitVar

Other links and lift over

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