Genetic Variant NM_032266.5:c.12266T>C (chr2-27578626-T-C) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.392

Publications

50 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=2.4241209E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31H1	NM_032266.5 link	c.12266T>C	p.Val4089Ala	missense_variant	Exon 5 of 5	ENST00000447166.3	NP_115642.4	Q68DN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA31H1	ENST00000447166.3 link	c.12266T>C	p.Val4089Ala	missense_variant	Exon 5 of 5	3	NM_032266.5	ENSP00000403181.2		C9JG08

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41961

AN:

151966

Hom.:

6332

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.272

AC XY:

197757

AN XY:

726962

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

16372

32743

49115

65486

81858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9792

19584

29376

39168

48960

<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:

0.276

AC:

41972

AN:

152084

Hom.:

6335

Cov.:

AF XY:

0.281

AC XY:

20918

AN XY:

74352

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.272

AC:

18458

AN:

67978

Other (OTH)

AF:

0.325

AC:

686

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1526

3051

4577

6102

7628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.277

Hom.:

16961

Bravo

AF:

0.289

TwinsUK

AF:

0.255

AC:

947

ALSPAC

AF:

0.255

AC:

982

ESP6500AA

AF:

0.184

AC:

687

ESP6500EA

AF:

0.270

AC:

2218

ExAC

AF:

0.297

AC:

35861

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.42

T;T

MetaRNN

Benign

0.00024

T;T

MetaSVM

Benign

-1.0

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

Polyphen

0.41

.;B

Vest4

0.023

MPC

0.14

ClinPred

0.0039

GERP RS

1.8

Varity_R

0.045

gMVP

0.045

Mutation Taster

=96/4

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