7-83367390-A-T

Variant names:

• chr7-83367390-A-T
• rs3801661
• NM_012431.3:c.*196T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012431.3(SEMA3E):​c.*196T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 595,034 control chromosomes in the GnomAD database, including 3,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (717 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2490 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.100
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-83367390-A-T is Benign according to our data. Variant chr7-83367390-A-T is described in ClinVar as [Benign]. Clinvar id is 1233803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.*196T>A		3_prime_UTR_variant	Exon 17 of 17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.*196T>A		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.*196T>A		3_prime_UTR_variant	Exon 17 of 17		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000643441.1	n.*95T>A		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14350 AN: 152098 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.102 AC: 45270 AN: 442818 Hom.: 2490 Cov.: 5 AF XY: 0.102 AC XY: 23802 AN XY: 233762

African (AFR) AF: 0.0742 AC: 906 AN: 12206

American (AMR) AF: 0.110 AC: 1996 AN: 18134

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 2186 AN: 12986

East Asian (EAS) AF: 0.143 AC: 4154 AN: 29106

South Asian (SAS) AF: 0.0869 AC: 3635 AN: 41836

European-Finnish (FIN) AF: 0.0727 AC: 2044 AN: 28120

Middle Eastern (MID) AF: 0.161 AC: 305 AN: 1898

European-Non Finnish (NFE) AF: 0.100 AC: 27337 AN: 273398

Other (OTH) AF: 0.108 AC: 2707 AN: 25134

GnomAD4 genome AF: 0.0943 AC: 14353 AN: 152216 Hom.: 717 Cov.: 32 AF XY: 0.0952 AC XY: 7085 AN XY: 74424

African (AFR) AF: 0.0761 AC: 3159 AN: 41522

American (AMR) AF: 0.105 AC: 1603 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3468

East Asian (EAS) AF: 0.127 AC: 659 AN: 5180

South Asian (SAS) AF: 0.0841 AC: 406 AN: 4830

European-Finnish (FIN) AF: 0.0688 AC: 730 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6843 AN: 68002

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.0934 Hom.: 87

Bravo AF: 0.0965

Asia WGS AF: 0.0940 AC: 325 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.022
DANN	Benign	0.47
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs3801661; hg19: chr7-82996706;