Variant 2-96860976-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017789.5(SEMA4C):c.2152C>G(p.Pro718Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SEMA4C
NM_017789.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

SEMA4C (HGNC:10731): (semaphorin 4C) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4C links:

SEMA4C (HGNC:):

SEMA4C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06374988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4C	NM_017789.5 linkuse as main transcript	c.2152C>G	p.Pro718Ala	missense_variant	15/15	ENST00000305476.10	NP_060259.4	Q9C0C4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SEMA4C	ENST00000305476.10 linkuse as main transcript	c.2152C>G	p.Pro718Ala	missense_variant	15/15	1	NM_017789.5	ENSP00000306844.5	Q9C0C4
SEMA4C	ENST00000467747.1 linkuse as main transcript	n.2143C>G		non_coding_transcript_exon_variant	3/3	2
SEMA4C	ENST00000474420.1 linkuse as main transcript	n.1385C>G		non_coding_transcript_exon_variant	2/2	2
SEMA4C	ENST00000482925.5 linkuse as main transcript	n.2542C>G		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460690

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726640

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2022

The c.2152C>G (p.P718A) alteration is located in exon 15 (coding exon 14) of the SEMA4C gene. This alteration results from a C to G substitution at nucleotide position 2152, causing the proline (P) at amino acid position 718 to be replaced by an alanine (A). 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

0.061

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.080

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.59

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.66

M_CAP

Benign

0.024

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.81

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.090

REVEL

Benign

0.091

Sift

Benign

0.33

Sift4G

Benign

0.88

Polyphen

0.0010

Vest4

0.12

MutPred

0.24

Loss of glycosylation at P718 (P = 0.0239);

MVP

0.24

MPC

0.28

ClinPred

0.084

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over