rs59186128

Variant names:

• chr7-84160110-C-T
• rs59186128
• NM_006080.3:c.113-25159G>A

Variant summary

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

The NM_006080.3(SEMA3A):​c.113-25159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,002 control chromosomes in the GnomAD database, including 653 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 0.063 (653 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• 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, SD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia, 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 = 0.165 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. 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
	SEMA3A	NM_006080.3	MANE Select	c.113-25159G>A		intron	N/A	NP_006071.1	Q14563

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.113-25159G>A		intron	N/A	ENSP00000265362.3	Q14563
	SEMA3A	ENST00000436949.5	TSL:5	c.113-25159G>A		intron	N/A	ENSP00000415260.1	Q14563
	SEMA3A	ENST00000864988.1		c.113-25159G>A		intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes AF: 0.0627 AC: 9528 AN: 151884 Hom.: 650 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0608

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.00680

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0628 AC: 9547 AN: 152002 Hom.: 653 Cov.: 32 AF XY: 0.0615 AC XY: 4573 AN XY: 74320

African (AFR) AF: 0.168 AC: 6968 AN: 41394

American (AMR) AF: 0.0277 AC: 423 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0608 AC: 211 AN: 3468

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5178

South Asian (SAS) AF: 0.0730 AC: 352 AN: 4822

European-Finnish (FIN) AF: 0.00680 AC: 72 AN: 10582

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1282 AN: 67990

Other (OTH) AF: 0.0507 AC: 107 AN: 2110

Alfa AF: 0.0430 Hom.: 41

Bravo AF: 0.0687

Asia WGS AF: 0.0580 AC: 199 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.67
PhyloP100		-0.96
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: rs59186128; hg19: chr7-83789426;