Genetic Variant NM_012431.3:c.*256T>C (chr7-83367330-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012431.3(SEMA3E):c.*256T>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 0.0274 in 406,682 control chromosomes in the GnomAD database, including 1,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 929 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 159 hom. )

Consequence

SEMA3E
NM_012431.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0480

Publications

1 publications found

Variant links:

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

SEMA3E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-83367330-A-G is Benign according to our data. Variant chr7-83367330-A-G is described in ClinVar as [Benign]. Clinvar id is 1242507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3 link	c.*256T>C		3_prime_UTR_variant	Exon 17 of 17	ENST00000643230.2	NP_036563.1	O15041-1
SEMA3E	NM_001178129.2 link	c.*256T>C		3_prime_UTR_variant	Exon 17 of 17		NP_001171600.1	O15041-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 link	c.*256T>C		3_prime_UTR_variant	Exon 17 of 17		NM_012431.3	ENSP00000496491.1		O15041-1
SEMA3E	ENST00000643441.1 link	n.*155T>C		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9186

AN:

152134

Hom.:

928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0231

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0421

GnomAD4 exome

AF:

0.00750

AC:

1909

AN:

254430

Hom.:

159

Cov.:

AF XY:

0.00630

AC XY:

843

AN XY:

133914

show subpopulations

African (AFR)

AF:

0.185

AC:

1451

AN:

7854

American (AMR)

AF:

0.0136

AC:

137

AN:

10082

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8280

East Asian (EAS)

AF:

0.00

AC:

AN:

17314

South Asian (SAS)

AF:

0.000508

AC:

AN:

21662

European-Finnish (FIN)

AF:

0.0000753

AC:

AN:

13288

Middle Eastern (MID)

AF:

0.00442

AC:

AN:

1130

European-Non Finnish (NFE)

AF:

0.000376

AC:

AN:

159456

Other (OTH)

AF:

0.0159

AC:

244

AN:

15364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0605

AC:

9217

AN:

152252

Hom.:

929

Cov.:

AF XY:

0.0580

AC XY:

4320

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.210

AC:

8709

AN:

41494

American (AMR)

AF:

0.0231

AC:

353

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00103

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000897

AC:

AN:

68024

Other (OTH)

AF:

0.0416

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

378

756

1133

1511

1889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0190

Hom.:

444

Bravo

AF:

0.0694

Asia WGS

AF:

0.00985

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 22, 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

-0.85

CADD

Benign

1.6

(source)

DANN

Benign

0.53

PhyloP100

0.048

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_012431.3:c.*256T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over