Genetic Variant SPATA31H1:p.His4963Tyr (chr2-27581247-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_032266.5(SPATA31H1):c.14887C>T(p.His4963Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,244 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.0098 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 28 hom. )

Consequence

SPATA31H1
NM_032266.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

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=0.003415078).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00977 (1489/152350) while in subpopulation AFR AF = 0.033 (1374/41576). AF 95% confidence interval is 0.0316. There are 26 homozygotes in GnomAd4. There are 741 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA31H1	NM_032266.5 link	c.14887C>T	p.His4963Tyr	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
C2orf16	ENST00000447166.3 link	c.14887C>T	p.His4963Tyr	missense_variant	Exon 5 of 5	3	NM_032266.5	ENSP00000403181.2		C9JG08

Frequencies

GnomAD3 genomes

AF:

0.00972

AC:

1480

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00269

AC:

671

AN:

249460

AF XY:

0.00222

show subpopulations

Gnomad AFR exome

AF:

0.0339

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000300

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00115

AC:

1684

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

749

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0341

AC:

1140

AN:

33480

Gnomad4 AMR exome

AF:

0.00268

AC:

120

AN:

44724

Gnomad4 ASJ exome

AF:

0.000536

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000580

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.0000187

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.000206

AC:

229

AN:

1112012

Gnomad4 Remaining exome

AF:

0.00262

AC:

158

AN:

60396

Heterozygous variant carriers

123

246

369

492

615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.00977

AC:

1489

AN:

152350

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

741

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0330

AC:

0.0330479

AN:

0.0330479

Gnomad4 AMR

AF:

0.00464

AC:

0.00464052

AN:

0.00464052

Gnomad4 ASJ

AF:

0.000288

AC:

0.000288018

AN:

0.000288018

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000367

AC:

0.000367463

AN:

0.000367463

Gnomad4 OTH

AF:

0.00615

AC:

0.00614948

AN:

0.00614948

Heterozygous variant carriers

135

203

270

338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00414

Hom.:

Bravo

AF:

0.0107

ESP6500AA

AF:

0.0344

AC:

130

ESP6500EA

AF:

0.000365

AC:

ExAC

AF:

0.00301

AC:

364

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.029

DANN

Benign

0.61

DEOGEN2

Benign

0.0018

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.4

.;L

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.025

Sift

Benign

0.36

.;T

Sift4G

Benign

0.75

.;T

Polyphen

0.0010

.;B

Vest4

0.075

MVP

0.040

MPC

0.099

ClinPred

0.017

GERP RS

-5.8

Varity_R

0.035

gMVP

0.029

Mutation Taster

=96/4

polymorphism

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over