7-83367359-A-G

Variant names:

• chr7-83367359-A-G
• rs75632631
• NM_012431.3:c.*227T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012431.3(SEMA3E):​c.*227T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 507,554 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 0.0033 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (1 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.35
• Publications: 1 publications found

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]

SEMA3E Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Kallmann syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• CHARGE syndrome

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-83367359-A-G is Benign according to our data. Variant chr7-83367359-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1198930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 498 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.*227T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.*227T>C		3_prime_UTR_variant	Exon 17 of 17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*227T>C		3_prime_UTR_variant	Exon 17 of 17		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000643441.1	n.*126T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00327 AC: 498 AN: 152168 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000476 AC: 169 AN: 355268 Hom.: 1 Cov.: 4 AF XY: 0.000380 AC XY: 71 AN XY: 186946

African (AFR) AF: 0.0130 AC: 140 AN: 10750

American (AMR) AF: 0.000540 AC: 8 AN: 14808

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11172

East Asian (EAS) AF: 0.00 AC: 0 AN: 24072

South Asian (SAS) AF: 0.0000299 AC: 1 AN: 33398

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20362

Middle Eastern (MID) AF: 0.000626 AC: 1 AN: 1598

European-Non Finnish (NFE) AF: 0.00000917 AC: 2 AN: 218136

Other (OTH) AF: 0.000811 AC: 17 AN: 20972

GnomAD4 genome AF: 0.00327 AC: 498 AN: 152286 Hom.: 2 Cov.: 32 AF XY: 0.00310 AC XY: 231 AN XY: 74464

African (AFR) AF: 0.0115 AC: 478 AN: 41554

American (AMR) AF: 0.00105 AC: 16 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00173 Hom.: 1

Bravo AF: 0.00381

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.4
DANN	Benign	0.64
PhyloP100		3.4

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

Other links and lift over

dbSNP: rs75632631; hg19: chr7-82996675;