chr7-80748832-T-A

Variant names:

• chr7-80748832-T-A
• rs1405743
• NM_006379.5:c.1842+66A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006379.5(SEMA3C):​c.1842+66A>T variant causes a intron 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: 31)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SEMA3C NM_006379.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 7 publications found

Genes affected

SEMA3C (HGNC:10725): (semaphorin 3C) This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3C	NM_006379.5	c.1842+66A>T		intron_variant	Intron 17 of 17	ENST00000265361.8	NP_006370.1
SEMA3C	NM_001350120.2	c.1896+66A>T		intron_variant	Intron 17 of 17		NP_001337049.1
SEMA3C	NM_001350121.2	c.1668+66A>T		intron_variant	Intron 18 of 18		NP_001337050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3C	ENST00000265361.8	c.1842+66A>T		intron_variant	Intron 17 of 17	1	NM_006379.5	ENSP00000265361.3
SEMA3C	ENST00000419255.6	c.1842+66A>T		intron_variant	Intron 17 of 17	2		ENSP00000411193.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.53e-7 AC: 1 AN: 1328182 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 656420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29188

American (AMR) AF: 0.00 AC: 0 AN: 28966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20704

East Asian (EAS) AF: 0.00 AC: 0 AN: 37096

South Asian (SAS) AF: 0.00 AC: 0 AN: 68778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5182

European-Non Finnish (NFE) AF: 9.67e-7 AC: 1 AN: 1033774

Other (OTH) AF: 0.00 AC: 0 AN: 54646

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.013
DANN	Benign	0.59
PhyloP100		-1.1

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: rs1405743; hg19: chr7-80378148;