Genetic Variant SEMA6C:p.Arg713Gly (chr1-151133140-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 12/21 in silico tools predict 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Publications

2 publications found

Variant links:

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]

SEMA6C links:

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ACMG classification

Classification was made for transcript

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=0.18950212).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6C	NM_030913.6	MANE Select	c.2137C>G	p.Arg713Gly	missense	Exon 19 of 19	NP_112175.2
SEMA6C	NM_001178061.3		c.2233C>G	p.Arg745Gly	missense	Exon 20 of 20	NP_001171532.1	Q9H3T2-3
SEMA6C	NM_001178062.3		c.2113C>G	p.Arg705Gly	missense	Exon 19 of 19	NP_001171533.1	Q9H3T2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6C	ENST00000368914.8	TSL:1 MANE Select	c.2137C>G	p.Arg713Gly	missense	Exon 19 of 19	ENSP00000357910.3	Q9H3T2-1
SEMA6C	ENST00000368913.7	TSL:1	c.2233C>G	p.Arg745Gly	missense	Exon 20 of 20	ENSP00000357909.3	Q9H3T2-3
SEMA6C	ENST00000341697.7	TSL:1	c.2137C>G	p.Arg713Gly	missense	Exon 19 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000550

AC:

AN:

181810

AF XY:

0.00

show subpopulations

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:

7.10e-7

AC:

AN:

1408168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30544

American (AMR)

AF:

0.00

AC:

AN:

37818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23520

East Asian (EAS)

AF:

0.00

AC:

AN:

38048

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80448

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5534

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097228

Other (OTH)

AF:

0.00

AC:

AN:

58470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.069

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

3.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

REVEL

Benign

0.049

Sift

Uncertain

0.025

Sift4G

Uncertain

0.029

Polyphen

0.43

Vest4

0.23

MutPred

0.23

Loss of MoRF binding (P = 0.0084)

MVP

0.48

MPC

0.90

ClinPred

0.59

GERP RS

2.8

Varity_R

0.19

gMVP

0.30

Mutation Taster

=87/13

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over