rs61729608

Positions:

• chr7-83386996-T-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_012431.3(SEMA3E):​c.1722A>T​(p.Gly574=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,613,334 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (4 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0130

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-83386996-T-A is Benign according to our data. Variant chr7-83386996-T-A is described in ClinVar as [Benign]. Clinvar id is 240862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83386996-T-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.013 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00485 (739/152280) while in subpopulation AFR AF= 0.0167 (694/41570). AF 95% confidence interval is 0.0157. There are 6 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 739 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.1722A>T	p.Gly574=	synonymous_variant	15/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.1542A>T	p.Gly514=	synonymous_variant	15/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.1722A>T	p.Gly574=	synonymous_variant	15/17		NM_012431.3	ENSP00000496491	P1
SEMA3E	ENST00000642232.1	c.1722A>T	p.Gly574=	synonymous_variant	15/17			ENSP00000494064
SEMA3E	ENST00000643441.1	n.1707A>T		non_coding_transcript_exon_variant	15/17

Frequencies

GnomAD3 genomes AF: 0.00486 AC: 739 AN: 152162 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00121 AC: 302 AN: 250568 Hom.: 3 AF XY: 0.000908 AC XY: 123 AN XY: 135466

Gnomad AFR exome AF: 0.0167

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.000486 AC: 710 AN: 1461054 Hom.: 4 Cov.: 30 AF XY: 0.000428 AC XY: 311 AN XY: 726814

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.000843

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00485 AC: 739 AN: 152280 Hom.: 6 Cov.: 32 AF XY: 0.00461 AC XY: 343 AN XY: 74466

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00145 Hom.: 0

Bravo AF: 0.00562

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 12, 2020	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CHARGE syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.7
DANN	Benign	0.69

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: rs61729608; hg19: chr7-83016312;