dbSNP rs1319959990: SEMA6C:p.Pro786Ser (chr1-151132921-G-A) – 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.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. 13/21 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.185

Publications

0 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=0.06907171).

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.2356C>T	p.Pro786Ser	missense	Exon 19 of 19	NP_112175.2
SEMA6C	NM_001178061.3		c.2452C>T	p.Pro818Ser	missense	Exon 20 of 20	NP_001171532.1	Q9H3T2-3
SEMA6C	NM_001178062.3		c.2332C>T	p.Pro778Ser	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.2356C>T	p.Pro786Ser	missense	Exon 19 of 19	ENSP00000357910.3	Q9H3T2-1
SEMA6C	ENST00000368913.7	TSL:1	c.2452C>T	p.Pro818Ser	missense	Exon 20 of 20	ENSP00000357909.3	Q9H3T2-3
SEMA6C	ENST00000341697.7	TSL:1	c.2356C>T	p.Pro786Ser	missense	Exon 19 of 19	ENSP00000344148.3	Q9H3T2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.07e-7

AC:

AN:

1238882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

612326

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23144

American (AMR)

AF:

0.00

AC:

AN:

18250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18716

East Asian (EAS)

AF:

0.00

AC:

AN:

22504

South Asian (SAS)

AF:

0.00

AC:

AN:

69456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3804

European-Non Finnish (NFE)

AF:

9.96e-7

AC:

AN:

1003524

Other (OTH)

AF:

0.00

AC:

AN:

49154

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.65

M_CAP

Benign

0.032

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

PhyloP100

0.18

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.35

REVEL

Benign

0.073

Sift

Benign

0.23

Sift4G

Benign

0.61

Polyphen

0.034

Vest4

0.13

MutPred

0.14

Gain of phosphorylation at P786 (P = 0.0063)

MVP

0.39

MPC

1.1

ClinPred

0.18

GERP RS

2.5

Varity_R

0.047

gMVP

0.29

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over