NM_030913.6:c.2356C>G

Variant names:

• chr1-151132921-G-C
• rs1319959990
• NM_030913.6:c.2356C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030913.6(SEMA6C):​c.2356C>G​(p.Pro786Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000565 in 1,238,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P786S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 0 publications found

Genes affected

SEMA6C (HGNC:10740): (semaphorin 6C) This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07228339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030913.6. 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
	SEMA6C	NM_030913.6	MANE Select	c.2356C>G	p.Pro786Ala	missense	Exon 19 of 19	NP_112175.2
	SEMA6C	NM_001178061.3		c.2452C>G	p.Pro818Ala	missense	Exon 20 of 20	NP_001171532.1	Q9H3T2-3
	SEMA6C	NM_001178062.3		c.2332C>G	p.Pro778Ala	missense	Exon 19 of 19	NP_001171533.1	Q9H3T2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6C	ENST00000368914.8	TSL:1 MANE Select	c.2356C>G	p.Pro786Ala	missense	Exon 19 of 19	ENSP00000357910.3	Q9H3T2-1
	SEMA6C	ENST00000368913.7	TSL:1	c.2452C>G	p.Pro818Ala	missense	Exon 20 of 20	ENSP00000357909.3	Q9H3T2-3
	SEMA6C	ENST00000341697.7	TSL:1	c.2356C>G	p.Pro786Ala	missense	Exon 19 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000565 AC: 7 AN: 1238886 Hom.: 0 Cov.: 32 AF XY: 0.00000653 AC XY: 4 AN XY: 612328

African (AFR) AF: 0.00 AC: 0 AN: 23144

American (AMR) AF: 0.00 AC: 0 AN: 18250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18718

East Asian (EAS) AF: 0.00 AC: 0 AN: 22504

South Asian (SAS) AF: 0.00 AC: 0 AN: 69458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3804

European-Non Finnish (NFE) AF: 0.00000698 AC: 7 AN: 1003524

Other (OTH) AF: 0.00 AC: 0 AN: 49154

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.18
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.074
Sift	Benign	0.17	T
Sift4G	Benign	0.56	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.16		Loss of catalytic residue at P786 (P = 0.0046)
MVP		0.38
MPC		0.99
ClinPred		0.084	T
GERP RS		2.5
Varity_R		0.048
gMVP		0.27
Mutation Taster		=88/12	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1319959990; hg19: chr1-151105397;