NM_006080.3:c.113-8148A>G

Variant names:

• chr7-84143099-T-C
• rs447
• NM_006080.3:c.113-8148A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006080.3(SEMA3A):​c.113-8148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.827 in 152,084 control chromosomes in the GnomAD database, including 52,180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52180 hom., cov: 31)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.113-8148A>G		intron_variant	Intron 1 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.113-8148A>G		intron_variant	Intron 4 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.113-8148A>G		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.113-8148A>G		intron_variant	Intron 1 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.113-8148A>G		intron_variant	Intron 2 of 17	5		ENSP00000415260.1
SEMA3A	ENST00000420047.1	c.113-8148A>G		intron_variant	Intron 2 of 4	4		ENSP00000391900.1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125726 AN: 151966 Hom.: 52148 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.834

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.827 AC: 125814 AN: 152084 Hom.: 52180 Cov.: 31 AF XY: 0.830 AC XY: 61701 AN XY: 74340

African (AFR) AF: 0.874 AC: 36251 AN: 41484

American (AMR) AF: 0.864 AC: 13168 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2903 AN: 3468

East Asian (EAS) AF: 0.945 AC: 4882 AN: 5166

South Asian (SAS) AF: 0.776 AC: 3743 AN: 4824

European-Finnish (FIN) AF: 0.793 AC: 8398 AN: 10592

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53735 AN: 67982

Other (OTH) AF: 0.829 AC: 1753 AN: 2114

Alfa AF: 0.829 Hom.: 24226

Bravo AF: 0.837

Asia WGS AF: 0.826 AC: 2875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.84
PhyloP100		-0.29
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: rs447; hg19: chr7-83772415;