NM_006080.3:c.1361-91_1361-88delCTTT

Variant names:

• chr7-84002133-CAAAG-C
• rs3832523
• NM_006080.3:c.1361-91_1361-88delCTTT

Variant summary

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

The NM_006080.3(SEMA3A):​c.1361-91_1361-88delCTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 717,676 control chromosomes in the GnomAD database, including 21,059 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4271 hom., cov: 24)
  • Exomes 𝑓: 0.24 (16788 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04
• Publications: 2 publications found

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hypogonadotropic hypogonadism 16 with or without anosmia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP6: Variant 7-84002133-CAAAG-C is Benign according to our data. Variant chr7-84002133-CAAAG-C is described in ClinVar as Benign. ClinVar VariationId is 1248345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1361-91_1361-88delCTTT		intron_variant	Intron 11 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1361-91_1361-88delCTTT		intron_variant	Intron 14 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1361-91_1361-88delCTTT		intron_variant	Intron 15 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-91_1361-88delCTTT		intron_variant	Intron 11 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1361-91_1361-88delCTTT		intron_variant	Intron 12 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35577 AN: 151796 Hom.: 4272 Cov.: 24

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.238 AC: 134744 AN: 565762 Hom.: 16788 AF XY: 0.242 AC XY: 72362 AN XY: 299540

African (AFR) AF: 0.238 AC: 3236 AN: 13574

American (AMR) AF: 0.178 AC: 3505 AN: 19654

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 3668 AN: 14932

East Asian (EAS) AF: 0.171 AC: 5230 AN: 30530

South Asian (SAS) AF: 0.323 AC: 14225 AN: 44062

European-Finnish (FIN) AF: 0.300 AC: 13269 AN: 44284

Middle Eastern (MID) AF: 0.329 AC: 1243 AN: 3778

European-Non Finnish (NFE) AF: 0.228 AC: 83495 AN: 365838

Other (OTH) AF: 0.236 AC: 6873 AN: 29110

GnomAD4 genome AF: 0.234 AC: 35586 AN: 151914 Hom.: 4271 Cov.: 24 AF XY: 0.238 AC XY: 17668 AN XY: 74246

African (AFR) AF: 0.239 AC: 9892 AN: 41460

American (AMR) AF: 0.202 AC: 3076 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 866 AN: 3466

East Asian (EAS) AF: 0.161 AC: 828 AN: 5142

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3149 AN: 10532

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.228 AC: 15474 AN: 67928

Other (OTH) AF: 0.227 AC: 477 AN: 2104

Alfa AF: 0.237 Hom.: 542

Bravo AF: 0.226

Asia WGS AF: 0.233 AC: 812 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: 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
PhyloP100		2.0
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: rs3832523; hg19: chr7-83631449;