SPATA31H1 p.Val4089Ala

Variant names:

• chr2-27578626-T-C
• rs1919127
• NM_032266.5:c.12266T>C
• SPATA31H1 p.Val4089Ala

Your query was ambiguous. Multiple possible variants found:

• chr2-27578626-T-C
• chr2-27578626-TG-CT
• chr2-27578626-TG-CC
• chr2-27578626-TG-CA

Variant summary

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

The NM_032266.5(SPATA31H1):​c.12266T>C​(p.Val4089Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,376 control chromosomes in the GnomAD database, including 65,269 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6335 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58934 hom.)
• Consequence: SPATA31H1 NM_032266.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392
• Publications: 50 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.4241209E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032266.5. 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
	SPATA31H1	NM_032266.5	MANE Select	c.12266T>C	p.Val4089Ala	missense	Exon 5 of 5	NP_115642.4	C9JG08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA31H1	ENST00000447166.3	TSL:3 MANE Select	c.12266T>C	p.Val4089Ala	missense	Exon 5 of 5	ENSP00000403181.2	C9JG08

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41961 AN: 151966 Hom.: 6332 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.312 AC: 77801 AN: 248980 AF XY: 0.299

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.311

GnomAD4 exome AF: 0.274 AC: 400940 AN: 1461292 Hom.: 58934 Cov.: 44 AF XY: 0.272 AC XY: 197757 AN XY: 726962

African (AFR) AF: 0.181 AC: 6057 AN: 33460

American (AMR) AF: 0.514 AC: 22957 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8822 AN: 26122

East Asian (EAS) AF: 0.535 AC: 21229 AN: 39688

South Asian (SAS) AF: 0.200 AC: 17251 AN: 86246

European-Finnish (FIN) AF: 0.285 AC: 15230 AN: 53396

Middle Eastern (MID) AF: 0.319 AC: 1838 AN: 5768

European-Non Finnish (NFE) AF: 0.261 AC: 290383 AN: 1111532

Other (OTH) AF: 0.284 AC: 17173 AN: 60380

GnomAD4 genome AF: 0.276 AC: 41972 AN: 152084 Hom.: 6335 Cov.: 32 AF XY: 0.281 AC XY: 20918 AN XY: 74352

African (AFR) AF: 0.191 AC: 7943 AN: 41502

American (AMR) AF: 0.451 AC: 6883 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1177 AN: 3472

East Asian (EAS) AF: 0.489 AC: 2524 AN: 5162

South Asian (SAS) AF: 0.199 AC: 957 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3071 AN: 10564

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18458 AN: 67978

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.277 Hom.: 16961

Bravo AF: 0.289

Asia WGS AF: 0.303 AC: 1056 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.00024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.39
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.027
Sift	Benign	0.30	T
Sift4G	Benign	0.43	T
Varity_R		0.045
gMVP		0.045
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1919127;

hg19: chr2-27801493;

COSMIC: COSV62673851;

COSMIC: COSV62673851;