1-151139661-C-G

Variant names:

• chr1-151139661-C-G
• rs1038942289
• NM_030913.6:c.274G>C

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.274G>C​(p.Gly92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,607,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

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=0.10392922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6C	NM_030913.6	c.274G>C	p.Gly92Arg	missense_variant	Exon 5 of 19	ENST00000368914.8	NP_112175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6C	ENST00000368914.8	c.274G>C	p.Gly92Arg	missense_variant	Exon 5 of 19	1	NM_030913.6	ENSP00000357910.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1454936 Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 4 AN XY: 722348

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 33354

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 44412

Gnomad4 ASJ exome AF: 0.000309 AC: 8 AN: 25926

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39510

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 85798

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53324

Gnomad4 NFE exome AF: 0.00 AC: 0 AN: 1106818

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 60038

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.000288 AC: 0.000288018 AN: 0.000288018

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.00 AC: 0 AN: 0

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.274G>C (p.G92R) alteration is located in exon 5 (coding exon 3) of the SEMA6C gene. This alteration results from a G to C substitution at nucleotide position 274, causing the glycine (G) at amino acid position 92 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	21
DANN	Benign	0.84
DEOGEN2	Benign	0.021	.;.;T;T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.83	T;T;.;T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.40	N;N;N;N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.16	N;N;N;N;.;.
REVEL	Benign	0.026
Sift	Benign	0.29	T;T;T;T;.;.
Sift4G	Benign	0.53	T;T;T;T;T;T
Polyphen		0.0010	B;B;B;B;.;.
Vest4		0.38
MutPred		0.46		Gain of solvent accessibility (P = 0.0471);Gain of solvent accessibility (P = 0.0471);Gain of solvent accessibility (P = 0.0471);Gain of solvent accessibility (P = 0.0471);Gain of solvent accessibility (P = 0.0471);Gain of solvent accessibility (P = 0.0471);
MVP		0.43
MPC		1.4
ClinPred		0.27	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.64
Mutation Taster		=91/9	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1038942289; hg19: chr1-151112137;