rs10487865

Positions:

• chr7-83981410-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_006080.3(SEMA3A):​c.1563G>C​(p.Gly521=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 1,613,724 control chromosomes in the GnomAD database, including 2,323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (165 hom., cov: 32)
  • Exomes 𝑓: 0.030 (2158 hom.)
• Consequence: SEMA3A NM_006080.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.202

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 Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 7-83981410-C-G is Benign according to our data. Variant chr7-83981410-C-G is described in ClinVar as [Benign]. Clinvar id is 1262671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83981410-C-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.202 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.1563G>C	p.Gly521=	synonymous_variant	14/17	ENST00000265362.9
SEMA3A	XM_005250110.4	c.1563G>C	p.Gly521=	synonymous_variant	17/20
SEMA3A	XM_047419751.1	c.1563G>C	p.Gly521=	synonymous_variant	18/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1563G>C	p.Gly521=	synonymous_variant	14/17	1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.1563G>C	p.Gly521=	synonymous_variant	15/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3932 AN: 152086 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.0308

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0282

GnomAD3 exomes AF: 0.0505 AC: 12670 AN: 250762 Hom.: 750 AF XY: 0.0500 AC XY: 6773 AN XY: 135572

Gnomad AFR exome AF: 0.00881

Gnomad AMR exome AF: 0.0976

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.184

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.00301

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0390

GnomAD4 exome AF: 0.0300 AC: 43847 AN: 1461520 Hom.: 2158 Cov.: 31 AF XY: 0.0318 AC XY: 23122 AN XY: 727056

Gnomad4 AFR exome AF: 0.00947

Gnomad4 AMR exome AF: 0.0925

Gnomad4 ASJ exome AF: 0.0299

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.00348

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0354

GnomAD4 genome AF: 0.0259 AC: 3935 AN: 152204 Hom.: 165 Cov.: 32 AF XY: 0.0284 AC XY: 2115 AN XY: 74408

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0308

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0191 Hom.: 18

Bravo AF: 0.0274

Asia WGS AF: 0.160 AC: 559 AN: 3478

EpiCase AF: 0.0167

EpiControl AF: 0.0178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	4.8
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs10487865; hg19: chr7-83610726; COSMIC: COSV54872435;