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

68 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31H1	NM_032266.5 link	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
SPATA31H1	ENST00000447166.3 link	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.:

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 v4.3

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

.;T

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.079

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.50

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

.;L

PhyloP100

2.3

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over