rs56204206

Variant names:

• chr15-74411928-C-A
• rs56204206
• NM_003612.5:c.1379G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-74411928-C-A
• chr15-74411928-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003612.5(SEMA7A):​c.1379G>T​(p.Arg460Leu) 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 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R460H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SEMA7A NM_003612.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12071535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA7A	NM_003612.5	c.1379G>T	p.Arg460Leu	missense_variant	Exon 11 of 14	ENST00000261918.9	NP_003603.1
SEMA7A	NM_001146029.3	c.1337G>T	p.Arg446Leu	missense_variant	Exon 10 of 13		NP_001139501.1
SEMA7A	NM_001146030.3	c.884G>T	p.Arg295Leu	missense_variant	Exon 11 of 14		NP_001139502.1
SEMA7A	XM_047433177.1	c.1256G>T	p.Arg419Leu	missense_variant	Exon 11 of 14		XP_047289133.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA7A	ENST00000261918.9	c.1379G>T	p.Arg460Leu	missense_variant	Exon 11 of 14	1	NM_003612.5	ENSP00000261918.4
SEMA7A	ENST00000543145.6	c.1337G>T	p.Arg446Leu	missense_variant	Exon 10 of 13	2		ENSP00000438966.2
SEMA7A	ENST00000542748.6	c.884G>T	p.Arg295Leu	missense_variant	Exon 11 of 14	5		ENSP00000441493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461680 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53220

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	T;T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.85	D;T;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.;.
PhyloP100		-0.36
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.7	D;D;N
REVEL	Benign	0.029
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.32
MutPred		0.36		Loss of catalytic residue at R460 (P = 0.0713);.;.;
MVP		0.30
MPC		0.59
ClinPred		0.16	T
GERP RS		-0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.35
Mutation Taster		=88/12	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

Other links and lift over

dbSNP: rs56204206; hg19: chr15-74704269;