rs6955597

Variant names:

• chr7-84129031-C-A
• rs6955597
• NM_006080.3:c.333+92G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-84129031-C-A
• chr7-84129031-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006080.3(SEMA3A):​c.333+92G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 997,558 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0066 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.81
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 7-84129031-C-A is Benign according to our data. Variant chr7-84129031-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1208050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00658 (1001/152046) while in subpopulation AFR AF = 0.0207 (860/41480). AF 95% confidence interval is 0.0196. There are 13 homozygotes in GnomAd4. There are 463 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR,AD,SD gene

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.333+92G>T		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.333+92G>T		intron	N/A	ENSP00000265362.3	Q14563
	SEMA3A	ENST00000436949.5	TSL:5	c.333+92G>T		intron	N/A	ENSP00000415260.1	Q14563
	SEMA3A	ENST00000864988.1		c.333+92G>T		intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes AF: 0.00654 AC: 994 AN: 151928 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00119 AC: 1006 AN: 845512 Hom.: 4 AF XY: 0.00115 AC XY: 509 AN XY: 443902

African (AFR) AF: 0.0189 AC: 393 AN: 20826

American (AMR) AF: 0.00287 AC: 117 AN: 40784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21064

East Asian (EAS) AF: 0.0000554 AC: 2 AN: 36122

South Asian (SAS) AF: 0.00235 AC: 164 AN: 69784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50284

Middle Eastern (MID) AF: 0.00421 AC: 19 AN: 4510

European-Non Finnish (NFE) AF: 0.000354 AC: 199 AN: 562342

Other (OTH) AF: 0.00281 AC: 112 AN: 39796

GnomAD4 genome AF: 0.00658 AC: 1001 AN: 152046 Hom.: 13 Cov.: 32 AF XY: 0.00623 AC XY: 463 AN XY: 74336

African (AFR) AF: 0.0207 AC: 860 AN: 41480

American (AMR) AF: 0.00557 AC: 85 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67974

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.00741

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.054
DANN	Benign	0.16
PhyloP100		-5.8
Mutation Taster		=100/0	polymorphism

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: rs6955597; hg19: chr7-83758347;