7-84060023-T-A

Variant names:

• chr7-84060023-T-A
• rs1357813
• NM_006080.3:c.547+442A>T

Variant summary

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

The NM_006080.3(SEMA3A):​c.547+442A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,096 control chromosomes in the GnomAD database, including 6,620 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 0.29 (6620 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.547+442A>T		intron_variant	Intron 5 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.547+442A>T		intron_variant	Intron 8 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.547+442A>T		intron_variant	Intron 9 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.547+442A>T		intron_variant	Intron 5 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.547+442A>T		intron_variant	Intron 6 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43316 AN: 151980 Hom.: 6613 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.285 AC: 43360 AN: 152096 Hom.: 6620 Cov.: 33 AF XY: 0.287 AC XY: 21346 AN XY: 74356

African (AFR) AF: 0.391 AC: 16216 AN: 41474

American (AMR) AF: 0.284 AC: 4338 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3472

East Asian (EAS) AF: 0.140 AC: 723 AN: 5176

South Asian (SAS) AF: 0.354 AC: 1706 AN: 4818

European-Finnish (FIN) AF: 0.225 AC: 2375 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16105 AN: 67988

Other (OTH) AF: 0.275 AC: 581 AN: 2116

Alfa AF: 0.272 Hom.: 749

Bravo AF: 0.292

Asia WGS AF: 0.255 AC: 891 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.55
PhyloP100		-0.97
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: rs1357813; hg19: chr7-83689339;