dbSNP rs1919128: SPATA31H1:p.Ile4178Val (chr2-27578892-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 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 0.24 ( 5642 hom., cov: 32)

Exomes 𝑓: 0.27 ( 58203 hom. )

Consequence

SPATA31H1
NM_032266.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28

Publications

69 publications found

Variant links:

Genes affected

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

SPATA31H1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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.12532A>G	p.Ile4178Val	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.12532A>G	p.Ile4178Val	missense	Exon 5 of 5	ENSP00000403181.2	C9JG08

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36777

AN:

151968

Hom.:

5638

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.304

AC:

75801

AN:

249398

AF XY:

0.293

show subpopulations

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 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.:

AF XY:

0.269

AC XY:

195813

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.0618

AC:

2070

AN:

33474

American (AMR)

AF:

0.506

AC:

22629

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

8826

AN:

26128

East Asian (EAS)

AF:

0.535

AC:

21228

AN:

39682

South Asian (SAS)

AF:

0.200

AC:

17243

AN:

86250

European-Finnish (FIN)

AF:

0.285

AC:

15248

AN:

53408

Middle Eastern (MID)

AF:

0.315

AC:

1817

AN:

5766

European-Non Finnish (NFE)

AF:

0.261

AC:

290450

AN:

1111594

Other (OTH)

AF:

0.277

AC:

16707

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

16796

33592

50388

67184

83980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9732

19464

29196

38928

48660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.242

AC:

36790

AN:

152088

Hom.:

5642

Cov.:

AF XY:

0.249

AC XY:

18522

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0728

AC:

3025

AN:

41544

American (AMR)

AF:

0.436

AC:

6652

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1177

AN:

3472

East Asian (EAS)

AF:

0.490

AC:

2535

AN:

5174

South Asian (SAS)

AF:

0.199

AC:

956

AN:

4814

European-Finnish (FIN)

AF:

0.292

AC:

3080

AN:

10546

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18469

AN:

67968

Other (OTH)

AF:

0.296

AC:

625

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1306

2611

3917

5222

6528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.266

Hom.:

21748

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00087

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

PhyloP100

2.3

PROVEAN

Benign

-0.41

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.97

Vest4

0.057

MPC

0.39

ClinPred

0.057

GERP RS

1.2

Varity_R

0.13

gMVP

0.056

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over