rs186628513

chr7-83387038-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012431.3(SEMA3E):c.1680A>G(p.Arg560=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 1,613,252 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (3 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.849

Genes affected

SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-83387038-T-C is Benign according to our data. Variant chr7-83387038-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 529142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.849 with no splicing effect.
• BS2: High AC in GnomAd at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.1680A>G	p.Arg560=	synonymous_variant	15/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.1500A>G	p.Arg500=	synonymous_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.1680A>G	p.Arg560=	synonymous_variant	15/17		NM_012431.3	P1
SEMA3E	ENST00000642232.1	c.1680A>G	p.Arg560=	synonymous_variant	15/17
SEMA3E	ENST00000643441.1	n.1665A>G		non_coding_transcript_exon_variant	15/17

Frequencies

GnomAD3 genomes AF: 0.000618 AC: 94 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000935 AC: 234 AN: 250398 Hom.: 1 AF XY: 0.000909 AC XY: 123 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00316

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00464

Gnomad NFE exome AF: 0.000531

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000472 AC: 690 AN: 1461004 Hom.: 3 Cov.: 30 AF XY: 0.000440 AC XY: 320 AN XY: 726812

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00407

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00388

Gnomad4 NFE exome AF: 0.000227

Gnomad4 OTH exome AF: 0.000779

GnomAD4 genome AF: 0.000617 AC: 94 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000820 AC XY: 61 AN XY: 74432

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000528 Hom.: 0

Bravo AF: 0.000283

Asia WGS AF: 0.00318 AC: 11 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHARGE syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

CHARGE syndrome;C0342384:Hypogonadotropic hypogonadism 7 with or without anosmia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 10, 2021

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	8.3
Dann	Benign	0.69

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: rs186628513; hg19: chr7-83016354; COSMIC: COSV57083531;