7-83367517-GATTT-GATTTATTT

Variant names:

• chr7-83367517-G-GATTT
• rs5885345
• NM_012431.3:c.*65_*68dupAAAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012431.3(SEMA3E):​c.*65_*68dupAAAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,486,050 control chromosomes in the GnomAD database, including 1,630 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (898 hom., cov: 31)
  • Exomes 𝑓: 0.0060 (732 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.206
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-83367517-G-GATTT is Benign according to our data. Variant chr7-83367517-G-GATTT is described in ClinVar as Benign. ClinVar VariationId is 1236886.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 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.*65_*68dupAAAT		3_prime_UTR	Exon 17 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.*65_*68dupAAAT		3_prime_UTR	Exon 17 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.*65_*68dupAAAT		3_prime_UTR	Exon 17 of 17	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000643441.1		n.2378_2381dupAAAT		non_coding_transcript_exon	Exon 17 of 17
	SEMA3E	ENST00000891111.1		c.*65_*68dupAAAT		downstream_gene	N/A	ENSP00000561170.1

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9106 AN: 151964 Hom.: 897 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.00604 AC: 8058 AN: 1333968 Hom.: 732 Cov.: 22 AF XY: 0.00523 AC XY: 3508 AN XY: 670602

African (AFR) AF: 0.209 AC: 6298 AN: 30168

American (AMR) AF: 0.0126 AC: 560 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25340

East Asian (EAS) AF: 0.00 AC: 0 AN: 39114

South Asian (SAS) AF: 0.000481 AC: 40 AN: 83182

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53346

Middle Eastern (MID) AF: 0.00650 AC: 36 AN: 5536

European-Non Finnish (NFE) AF: 0.000354 AC: 353 AN: 996648

Other (OTH) AF: 0.0137 AC: 769 AN: 56148

GnomAD4 genome AF: 0.0601 AC: 9137 AN: 152082 Hom.: 898 Cov.: 31 AF XY: 0.0576 AC XY: 4281 AN XY: 74360

African (AFR) AF: 0.209 AC: 8631 AN: 41384

American (AMR) AF: 0.0230 AC: 351 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

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

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

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68008

Other (OTH) AF: 0.0417 AC: 88 AN: 2112

Alfa AF: 0.0536 Hom.: 37

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5885345; hg19: chr7-82996833;