Genetic Variant SPATA31H1:p.Leu4621Ser (chr2-27580222-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032266.5(SPATA31H1):c.13862T>C(p.Leu4621Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,614,194 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0060 ( 50 hom. )

Consequence

SPATA31H1
NM_032266.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.41

Publications

10 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003681302).

BP6

Variant 2-27580222-T-C is Benign according to our data. Variant chr2-27580222-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650774.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

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.13862T>C	p.Leu4621Ser	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.13862T>C	p.Leu4621Ser	missense	Exon 5 of 5	ENSP00000403181.2	C9JG08

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

762

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0965

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00672

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00541

AC:

1349

AN:

249470

AF XY:

0.00601

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.00445

Gnomad NFE exome

AF:

0.00696

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00596

AC:

8709

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

4395

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33480

American (AMR)

AF:

0.00246

AC:

110

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

265

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00682

AC:

588

AN:

86258

European-Finnish (FIN)

AF:

0.00537

AC:

287

AN:

53412

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00636

AC:

7077

AN:

1112012

Other (OTH)

AF:

0.00553

AC:

334

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

527

1054

1580

2107

2634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.00501

AC:

763

AN:

152308

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41570

American (AMR)

AF:

0.00255

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00518

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00672

AC:

457

AN:

68014

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00547

Hom.:

Bravo

AF:

0.00477

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00106

AC:

ESP6500EA

AF:

0.00583

AC:

ExAC

AF:

0.00581

AC:

702

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00523

EpiControl

AF:

0.00646

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.00090

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

3.4

PROVEAN

Benign

-1.0

REVEL

Benign

0.041

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.025

Polyphen

0.12

Vest4

0.16

MVP

0.055

MPC

0.15

ClinPred

0.048

GERP RS

4.0

Varity_R

0.15

gMVP

0.051

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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