rs1013641087

Variant names:

• chr1-151132845-G-A
• rs1013641087
• NM_030913.6:c.2432C>T

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.2432C>T​(p.Pro811Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,283,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.101
• Publications: 2 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=0.08074176).

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.2432C>T	p.Pro811Leu	missense	Exon 19 of 19	NP_112175.2
	SEMA6C	NM_001178061.3		c.2528C>T	p.Pro843Leu	missense	Exon 20 of 20	NP_001171532.1	Q9H3T2-3
	SEMA6C	NM_001178062.3		c.2408C>T	p.Pro803Leu	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.2432C>T	p.Pro811Leu	missense	Exon 19 of 19	ENSP00000357910.3	Q9H3T2-1
	SEMA6C	ENST00000368913.7	TSL:1	c.2528C>T	p.Pro843Leu	missense	Exon 20 of 20	ENSP00000357909.3	Q9H3T2-3
	SEMA6C	ENST00000341697.7	TSL:1	c.2432C>T	p.Pro811Leu	missense	Exon 19 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes AF: 0.0000465 AC: 7 AN: 150580 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00174

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1620 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 42 AN: 1132442 Hom.: 0 Cov.: 29 AF XY: 0.0000475 AC XY: 26 AN XY: 547202

African (AFR) AF: 0.00 AC: 0 AN: 21504

American (AMR) AF: 0.000135 AC: 1 AN: 7412

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 34 AN: 13638

East Asian (EAS) AF: 0.00 AC: 0 AN: 22712

South Asian (SAS) AF: 0.00 AC: 0 AN: 42922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3014

European-Non Finnish (NFE) AF: 0.00000422 AC: 4 AN: 948924

Other (OTH) AF: 0.0000671 AC: 3 AN: 44690

GnomAD4 genome AF: 0.0000465 AC: 7 AN: 150580 Hom.: 0 Cov.: 32 AF XY: 0.0000408 AC XY: 3 AN XY: 73522

African (AFR) AF: 0.00 AC: 0 AN: 41270

American (AMR) AF: 0.00 AC: 0 AN: 15118

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 6 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67480

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.0000567

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.10
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.17	T
Polyphen		0.18	B
Vest4		0.11
MutPred		0.22		Loss of glycosylation at P811 (P = 0.0664)
MVP		0.65
MPC		0.43
ClinPred		0.45	T
GERP RS		3.3
Varity_R		0.070
gMVP		0.55
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1013641087; hg19: chr1-151105321;