Variant rs6897513 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024867.4(SPEF2):c.211A>C(p.Asn71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 1,613,278 control chromosomes in the GnomAD database, including 268,929 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27983 hom., cov: 32)

Exomes 𝑓: 0.57 ( 240946 hom. )

Consequence

SPEF2
NM_024867.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

SPEF2 (HGNC:26293): (sperm flagellar 2) Involved in sperm axoneme assembly. Located in sperm flagellum. Implicated in spermatogenic failure 43. [provided by Alliance of Genome Resources, Apr 2022]

SPEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4489497E-6).

BP6

Variant 5-35641480-A-C is Benign according to our data. Variant chr5-35641480-A-C is described in ClinVar as [Benign]. Clinvar id is 403471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPEF2	NM_024867.4 linkuse as main transcript	c.211A>C	p.Asn71His	missense_variant	3/37	ENST00000356031.8	NP_079143.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPEF2	ENST00000356031.8 linkuse as main transcript	c.211A>C	p.Asn71His	missense_variant	3/37	1	NM_024867.4	ENSP00000348314	P2	Q9C093-1

Frequencies

GnomAD3 genomes

AF:

0.601

AC:

91191

AN:

151820

Hom.:

27941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.682

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.545

Gnomad OTH

AF:

0.587

GnomAD3 exomes

AF:

0.608

AC:

152691

AN:

251144

Hom.:

47492

AF XY:

0.600

AC XY:

81516

AN XY:

135748

show subpopulations

Gnomad AFR exome

AF:

0.689

Gnomad AMR exome

AF:

0.742

Gnomad ASJ exome

AF:

0.565

Gnomad EAS exome

AF:

0.739

Gnomad SAS exome

AF:

0.659

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.545

Gnomad OTH exome

AF:

0.576

GnomAD4 exome

AF:

0.571

AC:

833989

AN:

1461340

Hom.:

240946

Cov.:

AF XY:

0.572

AC XY:

415497

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.689

Gnomad4 AMR exome

AF:

0.726

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.764

Gnomad4 SAS exome

AF:

0.658

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.549

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.601

AC:

91297

AN:

151938

Hom.:

27983

Cov.:

AF XY:

0.600

AC XY:

44563

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.649

Gnomad4 ASJ

AF:

0.572

Gnomad4 EAS

AF:

0.737

Gnomad4 SAS

AF:

0.676

Gnomad4 FIN

AF:

0.494

Gnomad4 NFE

AF:

0.545

Gnomad4 OTH

AF:

0.585

Alfa

AF:

0.560

Hom.:

62938

Bravo

AF:

0.616

TwinsUK

AF:

0.543

AC:

2014

ALSPAC

AF:

0.543

AC:

2092

ESP6500AA

AF:

0.690

AC:

3041

ESP6500EA

AF:

0.547

AC:

4707

ExAC

AF:

0.606

AC:

73558

Asia WGS

AF:

0.679

AC:

2361

AN:

3478

EpiCase

AF:

0.543

EpiControl

AF:

0.528

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Spermatogenic failure 43

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.036

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.22

DEOGEN2

Benign

0.0039

.;.;T;T;.;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.060

T;T;T;T;T;T

MetaRNN

Benign

0.0000014

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-2.5

N;.;.;N;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.37

PROVEAN

Benign

2.6

N;N;.;N;N;N

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;.;T;T;T

Sift4G

Benign

1.0

T;T;.;T;T;T

Polyphen

0.0

B;B;.;B;.;.

Vest4

0.053

MPC

0.030

ClinPred

0.0071

GERP RS

5.9

Varity_R

0.12

gMVP

0.13

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over