7-83392656-A-G

Variant names:

• chr7-83392656-A-G
• rs61636768
• NM_012431.3:c.1566T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012431.3(SEMA3E):​c.1566T>C​(p.Tyr522Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00709 in 1,613,842 control chromosomes in the GnomAD database, including 667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (320 hom., cov: 31)
  • Exomes 𝑓: 0.0041 (347 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.666
• 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):

• CHD7-related CHARGE syndrome

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• CHARGE syndrome

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

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

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-83392656-A-G is Benign according to our data. Variant chr7-83392656-A-G is described in ClinVar as Benign. ClinVar VariationId is 416919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.666 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	NM_012431.3	MANE Select	c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.1386T>C	p.Tyr462Tyr	synonymous	Exon 14 of 17	NP_001171600.1	O15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	ENST00000643230.2	MANE Select	c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000891111.1		c.1560T>C	p.Tyr520Tyr	synonymous	Exon 14 of 17	ENSP00000561170.1
	SEMA3E	ENST00000642232.1		c.1566T>C	p.Tyr522Tyr	synonymous	Exon 14 of 17	ENSP00000494064.1	A0A2R8YCX5

Frequencies

GnomAD3 genomes AF: 0.0353 AC: 5363 AN: 152028 Hom.: 315 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00949 AC: 2382 AN: 250944 AF XY: 0.00700

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.00680

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000891

Gnomad OTH exome AF: 0.00735

GnomAD4 exome AF: 0.00415 AC: 6059 AN: 1461696 Hom.: 347 Cov.: 34 AF XY: 0.00368 AC XY: 2677 AN XY: 727154

African (AFR) AF: 0.131 AC: 4372 AN: 33462

American (AMR) AF: 0.00765 AC: 342 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.000919 AC: 24 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86256

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.0203 AC: 117 AN: 5762

European-Non Finnish (NFE) AF: 0.000545 AC: 606 AN: 1111880

Other (OTH) AF: 0.00937 AC: 566 AN: 60390

GnomAD4 genome AF: 0.0354 AC: 5388 AN: 152146 Hom.: 320 Cov.: 31 AF XY: 0.0339 AC XY: 2523 AN XY: 74386

African (AFR) AF: 0.122 AC: 5074 AN: 41484

American (AMR) AF: 0.0138 AC: 210 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68014

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.0139 Hom.: 70

Bravo AF: 0.0408

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.00172

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	CHARGE syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.72
DANN	Benign	0.43
PhyloP100		-0.67
Mutation Taster		=93/7	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: rs61636768; hg19: chr7-83021972;