7-80745062-TGC-AGA

Variant names:

• chr7-80745062-TGC-AGA
• NM_006379.5:c.2086_2088delGCAinsTCT
• SEMA3C p.Ala696Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006379.5(SEMA3C):​c.2086_2088delGCAinsTCT​(p.Ala696Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A696T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA3C NM_006379.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006379.5. 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
	SEMA3C	NM_006379.5	MANE Select	c.2086_2088delGCAinsTCT	p.Ala696Ser	missense	N/A	NP_006370.1	Q99985-1
	SEMA3C	NM_001350120.2		c.2140_2142delGCAinsTCT	p.Ala714Ser	missense	N/A	NP_001337049.1
	SEMA3C	NM_001350121.2		c.1912_1914delGCAinsTCT	p.Ala638Ser	missense	N/A	NP_001337050.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3C	ENST00000265361.8	TSL:1 MANE Select	c.2086_2088delGCAinsTCT	p.Ala696Ser	missense	N/A	ENSP00000265361.3	Q99985-1
	SEMA3C	ENST00000953788.1		c.2260_2262delGCAinsTCT	p.Ala754Ser	missense	N/A	ENSP00000623847.1
	SEMA3C	ENST00000953787.1		c.2203_2205delGCAinsTCT	p.Ala735Ser	missense	N/A	ENSP00000623846.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-80374378;