NM_006080.3:c.112+63T>C

Variant names:

• chr7-84194412-A-G
• rs13231702
• NM_006080.3:c.112+63T>C

Variant summary

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

The NM_006080.3(SEMA3A):​c.112+63T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 1,071,794 control chromosomes in the GnomAD database, including 1,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (352 hom., cov: 31)
  • Exomes 𝑓: 0.052 (1520 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.190
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 7-84194412-A-G is Benign according to our data. Variant chr7-84194412-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.112+63T>C		intron_variant	Intron 1 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.112+63T>C		intron_variant	Intron 4 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.112+63T>C		intron_variant	Intron 5 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.112+63T>C		intron_variant	Intron 1 of 16	1	NM_006080.3	ENSP00000265362.3

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 9547 AN: 116604 Hom.: 351 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0422

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.000671

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0495

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0973

GnomAD4 exome AF: 0.0524 AC: 50038 AN: 955092 Hom.: 1520 AF XY: 0.0508 AC XY: 25108 AN XY: 494230

African (AFR) AF: 0.0949 AC: 2183 AN: 22996

American (AMR) AF: 0.0403 AC: 1657 AN: 41124

Ashkenazi Jewish (ASJ) AF: 0.0505 AC: 1035 AN: 20498

East Asian (EAS) AF: 0.0000278 AC: 1 AN: 35968

South Asian (SAS) AF: 0.0139 AC: 1007 AN: 72194

European-Finnish (FIN) AF: 0.0376 AC: 1904 AN: 50692

Middle Eastern (MID) AF: 0.0676 AC: 312 AN: 4614

European-Non Finnish (NFE) AF: 0.0597 AC: 39635 AN: 664026

Other (OTH) AF: 0.0536 AC: 2304 AN: 42980

GnomAD4 genome AF: 0.0818 AC: 9551 AN: 116702 Hom.: 352 Cov.: 31 AF XY: 0.0798 AC XY: 4552 AN XY: 57068

African (AFR) AF: 0.113 AC: 3802 AN: 33564

American (AMR) AF: 0.0643 AC: 801 AN: 12456

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 180 AN: 2696

East Asian (EAS) AF: 0.000673 AC: 3 AN: 4460

South Asian (SAS) AF: 0.0212 AC: 74 AN: 3488

European-Finnish (FIN) AF: 0.0495 AC: 386 AN: 7798

Middle Eastern (MID) AF: 0.119 AC: 26 AN: 218

European-Non Finnish (NFE) AF: 0.0823 AC: 4095 AN: 49754

Other (OTH) AF: 0.0973 AC: 156 AN: 1604

Alfa AF: 0.0663 Hom.: 49

Bravo AF: 0.0670

Asia WGS AF: 0.0140 AC: 51 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		0.19
PromoterAI		0.015	Neutral
Mutation Taster		=99/1	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: rs13231702; hg19: chr7-83823728;