Variant rs387907241 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003612.5(SEMA7A):c.1040G>T(p.Arg347Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SEMA7A
NM_003612.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

SEMA7A (HGNC:10741): (semaphorin 7A (JohnMiltonHagen blood group)) This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

SEMA7A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA7A	NM_003612.5 linkuse as main transcript	c.1040G>T	p.Arg347Leu	missense_variant	9/14	ENST00000261918.9	NP_003603.1	O75326-1B3KMH6
SEMA7A	NM_001146029.3 linkuse as main transcript	c.998G>T	p.Arg333Leu	missense_variant	8/13		NP_001139501.1	O75326-2B3KMH6
SEMA7A	NM_001146030.3 linkuse as main transcript	c.545G>T	p.Arg182Leu	missense_variant	9/14		NP_001139502.1	O75326F5GYX3B3KMH6
SEMA7A	XM_047433177.1 linkuse as main transcript	c.917G>T	p.Arg306Leu	missense_variant	9/14		XP_047289133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEMA7A	ENST00000261918.9 linkuse as main transcript	c.1040G>T	p.Arg347Leu	missense_variant	9/14	1	NM_003612.5	ENSP00000261918.4	O75326-1
SEMA7A	ENST00000543145.6 linkuse as main transcript	c.998G>T	p.Arg333Leu	missense_variant	8/13	2		ENSP00000438966.2	O75326-2
SEMA7A	ENST00000542748.6 linkuse as main transcript	c.545G>T	p.Arg182Leu	missense_variant	9/14	5		ENSP00000441493.1	F5GYX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251304

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000425

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

John Milton Hagen blood group system

Other:1

Affects, no assertion criteria provided

literature only

OMIM

Apr 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

0.0030

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.0089

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.52

N;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.045

D;T;D

Polyphen

0.82

P;.;.

Vest4

0.53

MutPred

0.53

Loss of sheet (P = 0.0228);.;.;

MVP

0.39

MPC

1.0

ClinPred

0.37

GERP RS

5.6

Varity_R

0.54

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.43

Position offset: -17

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