rs387907241

chr15-74414893-C-Achr15-74414893-C-T

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
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: 1.23

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]

ACMG classification

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	UniProt
SEMA7A	NM_003612.5	c.1040G>T	p.Arg347Leu	missense_variant	9/14	ENST00000261918.9
SEMA7A	NM_001146029.3	c.998G>T	p.Arg333Leu	missense_variant	8/13
SEMA7A	NM_001146030.3	c.545G>T	p.Arg182Leu	missense_variant	9/14
SEMA7A	XM_047433177.1	c.917G>T	p.Arg306Leu	missense_variant	9/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9	c.1040G>T	p.Arg347Leu	missense_variant	9/14	1	NM_003612.5	P1
SEMA7A	ENST00000543145.6	c.998G>T	p.Arg333Leu	missense_variant	8/13	2
SEMA7A	ENST00000542748.6	c.545G>T	p.Arg182Leu	missense_variant	9/14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251304 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135836

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: 3 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

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.: 32

Alfa AF: 0.0000425 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

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	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	33
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.012
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.52	N;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.40	T
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	T
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

Other links and lift over

dbSNP: rs387907241; hg19: chr15-74707234;