Variant 19-4543825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032108.4(SEMA6B):c.2443G>A(p.Asp815Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 1,214,464 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

SEMA6B
NM_032108.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.925

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18631777).

BS2

High AC in GnomAdExome4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6B	NM_032108.4 linkuse as main transcript	c.2443G>A	p.Asp815Asn	missense_variant	17/17	ENST00000586582.6	NP_115484.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6B	ENST00000586582.6 linkuse as main transcript	c.2443G>A	p.Asp815Asn	missense_variant	17/17	1	NM_032108.4	ENSP00000467290	P1	Q9H3T3-1
SEMA6B	ENST00000586965.1 linkuse as main transcript	c.1851+592G>A		intron_variant		1		ENSP00000465722		Q9H3T3-3
SEMA6B	ENST00000676793.1 linkuse as main transcript	c.2443G>A	p.Asp815Asn	missense_variant	17/17			ENSP00000503414	P1	Q9H3T3-1
SEMA6B	ENST00000677828.1 linkuse as main transcript	c.*1705G>A		3_prime_UTR_variant, NMD_transcript_variant	17/17			ENSP00000503277

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000884

AC:

AN:

1063570

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

502064

show subpopulations

Gnomad4 AFR exome

AF:

0.0000450

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:

0.000101

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150894

Hom.:

Cov.:

AF XY:

0.0000407

AC XY:

AN XY:

73702

show subpopulations

Gnomad4 AFR

AF:

0.0000487

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.2443G>A (p.D815N) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a G to A substitution at nucleotide position 2443, causing the aspartic acid (D) at amino acid position 815 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.54

D;D;D

PrimateAI

Pathogenic

0.90

Sift4G

Benign

0.33

Polyphen

0.95

Vest4

0.18

MutPred

0.066

Loss of loop (P = 0.0288);

MVP

0.068

MPC

3.0

ClinPred

0.87

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.33

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