1-151133140-G-C

Variant names:

• chr1-151133140-G-C
• rs200026035
• NM_030913.6:c.2137C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030913.6(SEMA6C):​c.2137C>G​(p.Arg713Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R713C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18950212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6C	NM_030913.6	c.2137C>G	p.Arg713Gly	missense_variant	Exon 19 of 19	ENST00000368914.8	NP_112175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6C	ENST00000368914.8	c.2137C>G	p.Arg713Gly	missense_variant	Exon 19 of 19	1	NM_030913.6	ENSP00000357910.3
SEMA6C	ENST00000368913.7	c.2233C>G	p.Arg745Gly	missense_variant	Exon 20 of 20	1		ENSP00000357909.3
SEMA6C	ENST00000341697.7	c.2137C>G	p.Arg713Gly	missense_variant	Exon 19 of 19	1		ENSP00000344148.3
SEMA6C	ENST00000368912.7	c.2113C>G	p.Arg705Gly	missense_variant	Exon 19 of 19	1		ENSP00000357908.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000550 AC: 1 AN: 181810 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 102420

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000424

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408168 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 699968

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;T;T
Eigen	Benign	-0.069
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.70	T;T;.;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;.;L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.049
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D
Polyphen		0.43	B;P;P;P
Vest4		0.23
MutPred		0.23		.;.;Loss of MoRF binding (P = 0.0084);Loss of MoRF binding (P = 0.0084);
MVP		0.48
MPC		0.90
ClinPred		0.59	D
GERP RS		2.8
Varity_R		0.19
gMVP		0.30

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200026035; hg19: chr1-151105616;