17-45255758-C-T

Position:

• chr17-45255758-C-T

Variant summary

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

The NM_152343.3(SPATA32):​c.424G>A​(p.Val142Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,613,816 control chromosomes in the GnomAD database, including 158,708 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 0.36 (11068 hom., cov: 31)
  • Exomes 𝑓: 0.45 (147640 hom.)
• Consequence: SPATA32 NM_152343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

Genes affected

SPATA32 (HGNC:26349): (spermatogenesis associated 32) Predicted to enable actin binding activity. Predicted to be involved in spermatogenesis. Predicted to be active in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K14-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.017949E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA32	NM_152343.3	c.424G>A	p.Val142Met	missense_variant	4/5	ENST00000331780.5	NP_689556.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA32	ENST00000331780.5	c.424G>A	p.Val142Met	missense_variant	4/5	1	NM_152343.3	ENSP00000331532.4

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54097 AN: 151854 Hom.: 11067 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.351

GnomAD3 exomes AF: 0.409 AC: 102708 AN: 251314 Hom.: 21842 AF XY: 0.415 AC XY: 56417 AN XY: 135830

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.428

Gnomad EAS exome AF: 0.325

Gnomad SAS exome AF: 0.431

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.457

Gnomad OTH exome AF: 0.408

GnomAD4 exome AF: 0.445 AC: 650946 AN: 1461844 Hom.: 147640 Cov.: 93 AF XY: 0.446 AC XY: 324116 AN XY: 727214

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.427

GnomAD4 genome AF: 0.356 AC: 54114 AN: 151972 Hom.: 11068 Cov.: 31 AF XY: 0.354 AC XY: 26321 AN XY: 74282

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.351

Alfa AF: 0.436 Hom.: 31798

Bravo AF: 0.344

TwinsUK AF: 0.476 AC: 1766

ALSPAC AF: 0.481 AC: 1853

ESP6500AA AF: 0.152 AC: 671

ESP6500EA AF: 0.460 AC: 3960

ExAC AF: 0.406 AC: 49343

Asia WGS AF: 0.354 AC: 1230 AN: 3478

EpiCase AF: 0.462

EpiControl AF: 0.458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.39	T
MetaRNN	Benign	0.00040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.025
Sift	Benign	0.26	T
Sift4G	Benign	0.12	T
Polyphen		0.89	P
Vest4		0.020
MPC		0.27
ClinPred		0.010	T
GERP RS		-3.8
Varity_R		0.042
gMVP		0.042

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: rs11651968; hg19: chr17-43333125; COSMIC: COSV59304516; COSMIC: COSV59304516;