NM_012431.3:c.337-11delT

Variant names:

• chr7-83466611-GA-G
• rs536827692
• NM_012431.3:c.337-11delT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_012431.3(SEMA3E):​c.337-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,609,948 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (2 hom.)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.07

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 -12 ACMG points.

• BP6: Variant 7-83466611-GA-G is Benign according to our data. Variant chr7-83466611-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 235213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.337-11delT		intron_variant	Intron 3 of 16	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.157-11delT		intron_variant	Intron 3 of 16		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.337-11delT		intron_variant	Intron 3 of 16		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000642232.1	c.337-11delT		intron_variant	Intron 3 of 16			ENSP00000494064.1
SEMA3E	ENST00000442159.3	n.293-11delT		intron_variant	Intron 3 of 5	5
SEMA3E	ENST00000643441.1	n.322-11delT		intron_variant	Intron 3 of 16

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 151728 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00138 AC: 342 AN: 247458 Hom.: 0 AF XY: 0.00148 AC XY: 199 AN XY: 134014

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000560

Gnomad FIN exome AF: 0.00184

Gnomad NFE exome AF: 0.00217

Gnomad OTH exome AF: 0.000993

GnomAD4 exome AF: 0.00196 AC: 2852 AN: 1458102 Hom.: 2 Cov.: 31 AF XY: 0.00190 AC XY: 1376 AN XY: 725498

Gnomad4 AFR exome AF: 0.000451

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000790

Gnomad4 FIN exome AF: 0.00151

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00143 AC: 217 AN: 151846 Hom.: 1 Cov.: 32 AF XY: 0.00138 AC XY: 102 AN XY: 74178

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.000983

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00143

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.000948

Bravo AF: 0.00127

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 18, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 12, 2023

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

CHARGE syndrome Benign:1

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs536827692; hg19: chr7-83095927;