dbSNP rs55637216: SEMA7A:p.Arg207Leu (chr15-74417376-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003612.5(SEMA7A):c.620G>T(p.Arg207Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,702 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEMA7A
NM_003612.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08385977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA7A	NM_003612.5 link	c.620G>T	p.Arg207Leu	missense_variant	Exon 6 of 14	ENST00000261918.9	NP_003603.1	O75326-1B3KMH6
SEMA7A	NM_001146029.3 link	c.578G>T	p.Arg193Leu	missense_variant	Exon 5 of 13		NP_001139501.1	O75326-2B3KMH6
SEMA7A	NM_001146030.3 link	c.125G>T	p.Arg42Leu	missense_variant	Exon 6 of 14		NP_001139502.1	O75326F5GYX3B3KMH6
SEMA7A	XM_047433177.1 link	c.497G>T	p.Arg166Leu	missense_variant	Exon 6 of 14		XP_047289133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEMA7A	ENST00000261918.9 link	c.620G>T	p.Arg207Leu	missense_variant	Exon 6 of 14	1	NM_003612.5	ENSP00000261918.4	O75326-1
SEMA7A	ENST00000543145.6 link	c.578G>T	p.Arg193Leu	missense_variant	Exon 5 of 13	2		ENSP00000438966.2	O75326-2
SEMA7A	ENST00000542748.6 link	c.125G>T	p.Arg42Leu	missense_variant	Exon 6 of 14	5		ENSP00000441493.1	F5GYX3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.051

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.21

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.084

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.2

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.098

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.0040

B;.;.

Vest4

0.38

MutPred

0.49

Loss of methylation at R207 (P = 0.0404);.;.;

MVP

0.13

MPC

0.58

ClinPred

0.12

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.32

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over