1-151132921-G-A

Position:

• chr1-151132921-G-A

Variant summary

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

The NM_030913.6(SEMA6C):​c.2356C>T​(p.Pro786Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,238,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.185

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=0.06907171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6C	NM_030913.6	c.2356C>T	p.Pro786Ser	missense_variant	19/19	ENST00000368914.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6C	ENST00000368914.8	c.2356C>T	p.Pro786Ser	missense_variant	19/19	1	NM_030913.6	P4
SEMA6C	ENST00000368913.7	c.2452C>T	p.Pro818Ser	missense_variant	20/20	1		A1
SEMA6C	ENST00000341697.7	c.2356C>T	p.Pro786Ser	missense_variant	19/19	1		P4
SEMA6C	ENST00000368912.7	c.2332C>T	p.Pro778Ser	missense_variant	19/19	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1238882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 612326

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.96e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.2452C>T (p.P818S) alteration is located in exon 20 (coding exon 18) of the SEMA6C gene. This alteration results from a C to T substitution at nucleotide position 2452, causing the proline (P) at amino acid position 818 to be replaced by a serine (S). 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	0.075
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.65	T;T;.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.35	N;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.034	B;B;D;D
Vest4		0.13
MutPred		0.14		.;.;Gain of phosphorylation at P786 (P = 0.0063);Gain of phosphorylation at P786 (P = 0.0063);
MVP		0.39
MPC		1.1
ClinPred		0.18	T
GERP RS		2.5
Varity_R		0.047
gMVP		0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1319959990; hg19: chr1-151105397;