Variant 19-4543896-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6

The NM_032108.4(SEMA6B):c.2372C>G(p.Pro791Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000332 in 1,204,242 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SEMA6B
NM_032108.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.08

Variant links:

Genes affected

SEMA6B (HGNC:10739): (semaphorin 6B) This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]

SEMA6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40113962).

BP6

Variant 19-4543896-G-C is Benign according to our data. Variant chr19-4543896-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1709918.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6B	NM_032108.4 linkuse as main transcript	c.2372C>G	p.Pro791Arg	missense_variant	17/17	ENST00000586582.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6B	ENST00000586582.6 linkuse as main transcript	c.2372C>G	p.Pro791Arg	missense_variant	17/17	1	NM_032108.4	P1	Q9H3T3-1
SEMA6B	ENST00000586965.1 linkuse as main transcript	c.1851+521C>G		intron_variant		1			Q9H3T3-3
SEMA6B	ENST00000676793.1 linkuse as main transcript	c.2372C>G	p.Pro791Arg	missense_variant	17/17			P1	Q9H3T3-1
SEMA6B	ENST00000677828.1 linkuse as main transcript	c.*1634C>G		3_prime_UTR_variant, NMD_transcript_variant	17/17

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000285

AC:

AN:

1053064

Hom.:

Cov.:

AF XY:

0.00000402

AC XY:

AN XY:

496970

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:

0.0000484

Gnomad4 NFE exome

AF:

0.00000111

Gnomad4 OTH exome

AF:

0.0000241

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73818

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.2372C>G (p.P791R) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a C to G substitution at nucleotide position 2372, causing the proline (P) at amino acid position 791 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Epilepsy, progressive myoclonic, 11

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

MGZ Medical Genetics Center

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.92

Sift4G

Benign

0.077

Polyphen

1.0

Vest4

0.41

MutPred

0.30

Gain of MoRF binding (P = 0.0025);

MVP

0.043

MPC

3.3

ClinPred

0.94

GERP RS

3.0

Varity_R

0.25

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over