rs10235789

Variant names:

• chr7-84027484-T-C
• rs10235789
• NM_006080.3:c.668-13133A>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.668-13133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,036 control chromosomes in the GnomAD database, including 12,868 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 0.39 (12868 hom., cov: 32)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 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.668-13133A>G		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.668-13133A>G		intron	N/A	ENSP00000265362.3	Q14563
	SEMA3A	ENST00000436949.5	TSL:5	c.668-13133A>G		intron	N/A	ENSP00000415260.1	Q14563
	SEMA3A	ENST00000864988.1		c.668-13133A>G		intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59241 AN: 151918 Hom.: 12863 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.390 AC: 59269 AN: 152036 Hom.: 12868 Cov.: 32 AF XY: 0.387 AC XY: 28741 AN XY: 74304

African (AFR) AF: 0.226 AC: 9376 AN: 41490

American (AMR) AF: 0.408 AC: 6231 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1393 AN: 3470

East Asian (EAS) AF: 0.123 AC: 638 AN: 5168

South Asian (SAS) AF: 0.277 AC: 1338 AN: 4826

European-Finnish (FIN) AF: 0.471 AC: 4969 AN: 10556

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33872 AN: 67940

Other (OTH) AF: 0.418 AC: 882 AN: 2110

Alfa AF: 0.460 Hom.: 68863

Bravo AF: 0.378

Asia WGS AF: 0.228 AC: 792 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.77
PhyloP100		-0.066
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: rs10235789; hg19: chr7-83656800;