7-83961401-G-T

Variant names:

• chr7-83961401-G-T
• rs561754532
• NM_006080.3:c.2286C>A

Variant summary

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

The NM_006080.3(SEMA3A):​c.2286C>A​(p.His762Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,152 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H762H) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

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 rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.2286C>A	p.His762Gln	missense_variant	Exon 17 of 17	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.2286C>A	p.His762Gln	missense_variant	Exon 20 of 20		XP_005250167.1
SEMA3A	XM_047419751.1	c.2286C>A	p.His762Gln	missense_variant	Exon 21 of 21		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.2286C>A	p.His762Gln	missense_variant	Exon 17 of 17	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.2286C>A	p.His762Gln	missense_variant	Exon 18 of 18	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D;D
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.16
Sift	Benign	0.14	T;T
Sift4G	Benign	0.065	T;T
Polyphen		0.91	P;P
Vest4		0.56
MutPred		0.31		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);
MVP		0.63
MPC		0.94
ClinPred		0.97	D
GERP RS		2.1
Varity_R		0.21
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs561754532; hg19: chr7-83590717;