rs200026035

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-151133140-G-A
• chr1-151133140-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030913.6(SEMA6C):​c.2137C>T​(p.Arg713Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000572 in 1,560,024 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00059 (1 hom.)
• Consequence: SEMA6C NM_030913.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09115487).

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.2137C>T	p.Arg713Cys	missense	Exon 19 of 19	NP_112175.2
	SEMA6C	NM_001178061.3		c.2233C>T	p.Arg745Cys	missense	Exon 20 of 20	NP_001171532.1	Q9H3T2-3
	SEMA6C	NM_001178062.3		c.2113C>T	p.Arg705Cys	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.2137C>T	p.Arg713Cys	missense	Exon 19 of 19	ENSP00000357910.3	Q9H3T2-1
	SEMA6C	ENST00000368913.7	TSL:1	c.2233C>T	p.Arg745Cys	missense	Exon 20 of 20	ENSP00000357909.3	Q9H3T2-3
	SEMA6C	ENST00000341697.7	TSL:1	c.2137C>T	p.Arg713Cys	missense	Exon 19 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes AF: 0.000435 AC: 66 AN: 151744 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000663

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000440 AC: 80 AN: 181810 AF XY: 0.000430

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.000437

GnomAD4 exome AF: 0.000587 AC: 826 AN: 1408168 Hom.: 1 Cov.: 33 AF XY: 0.000539 AC XY: 377 AN XY: 699968

African (AFR) AF: 0.000131 AC: 4 AN: 30544

American (AMR) AF: 0.00111 AC: 42 AN: 37818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38048

South Asian (SAS) AF: 0.00 AC: 0 AN: 80448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.000684 AC: 750 AN: 1097228

Other (OTH) AF: 0.000513 AC: 30 AN: 58470

GnomAD4 genome AF: 0.000435 AC: 66 AN: 151856 Hom.: 0 Cov.: 32 AF XY: 0.000458 AC XY: 34 AN XY: 74254

African (AFR) AF: 0.000217 AC: 9 AN: 41476

American (AMR) AF: 0.000720 AC: 11 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000663 AC: 45 AN: 67842

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.000416 Hom.: 0

Bravo AF: 0.000468

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000315 AC: 2

ExAC AF: 0.000279 AC: 32

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	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.28
MVP		0.54
MPC		1.3
ClinPred		0.21	T
GERP RS		2.8
Varity_R		0.19
gMVP		0.32
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs200026035; hg19: chr1-151105616;