rs34541339

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006080.3(SEMA3A):​c.705T>C​(p.Ser235Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

SEMA3A
NM_006080.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.847

Publications

1 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP7
Synonymous conserved (PhyloP=0.847 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA3ANM_006080.3 linkc.705T>C p.Ser235Ser synonymous_variant Exon 7 of 17 ENST00000265362.9 NP_006071.1 Q14563
SEMA3AXM_005250110.4 linkc.705T>C p.Ser235Ser synonymous_variant Exon 10 of 20 XP_005250167.1 Q14563
SEMA3AXM_047419751.1 linkc.705T>C p.Ser235Ser synonymous_variant Exon 11 of 21 XP_047275707.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA3AENST00000265362.9 linkc.705T>C p.Ser235Ser synonymous_variant Exon 7 of 17 1 NM_006080.3 ENSP00000265362.3 Q14563
SEMA3AENST00000436949.5 linkc.705T>C p.Ser235Ser synonymous_variant Exon 8 of 18 5 ENSP00000415260.1 Q14563

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
9.8
DANN
Benign
0.75
PhyloP100
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs34541339; hg19: chr7-83643630; API