chr2-27578892-A-G

Variant names:

• chr2-27578892-A-G
• rs1919128
• NM_032266.5:c.12532A>G

Variant summary

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

The NM_032266.5(SPATA31H1):​c.12532A>G​(p.Ile4178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,613,474 control chromosomes in the GnomAD database, including 63,845 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.24 (5642 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58203 hom.)
• Consequence: SPATA31H1 NM_032266.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

Genes affected

SPATA31H1 (HGNC:25275): (SPATA31 subfamily H member 1) Located in extracellular exosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011802316).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31H1	NM_032266.5	c.12532A>G	p.Ile4178Val	missense_variant	Exon 5 of 5	ENST00000447166.3	NP_115642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2orf16	ENST00000447166.3	c.12532A>G	p.Ile4178Val	missense_variant	Exon 5 of 5	3	NM_032266.5	ENSP00000403181.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36777 AN: 151968 Hom.: 5638 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.296

GnomAD3 exomes AF: 0.304 AC: 75801 AN: 249398 Hom.: 13582 AF XY: 0.293 AC XY: 39660 AN XY: 135310

Gnomad AFR exome AF: 0.0645

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.339

Gnomad EAS exome AF: 0.478

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.307

GnomAD4 exome AF: 0.271 AC: 396218 AN: 1461386 Hom.: 58203 Cov.: 50 AF XY: 0.269 AC XY: 195813 AN XY: 727028

Gnomad4 AFR exome AF: 0.0618

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.535

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.242 AC: 36790 AN: 152088 Hom.: 5642 Cov.: 32 AF XY: 0.249 AC XY: 18522 AN XY: 74330

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.296

Alfa AF: 0.275 Hom.: 10730

Bravo AF: 0.249

TwinsUK AF: 0.255 AC: 947

ALSPAC AF: 0.255 AC: 981

ESP6500AA AF: 0.0729 AC: 266

ESP6500EA AF: 0.271 AC: 2207

ExAC AF: 0.287 AC: 34624

Asia WGS AF: 0.297 AC: 1035 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.00087	.;T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0012	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	.;L
PROVEAN	Benign	-0.41	.;N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.016	.;D
Polyphen		0.97	.;D
Vest4		0.057
MPC		0.39
ClinPred		0.057	T
GERP RS		1.2
Varity_R		0.13
gMVP		0.056

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: rs1919128; hg19: chr2-27801759; COSMIC: COSV62673858; COSMIC: COSV62673858;