19-4543717-T-A

Position:

• chr19-4543717-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032108.4(SEMA6B):​c.2551A>T​(p.Ser851Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEMA6B NM_032108.4 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 1.26

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]

ACMG classification

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=0.25075704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6B	NM_032108.4	c.2551A>T	p.Ser851Cys	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	c.2551A>T	p.Ser851Cys	missense_variant	17/17	1	NM_032108.4	ENSP00000467290	P1
SEMA6B	ENST00000586965.1	c.1852-621A>T		intron_variant		1		ENSP00000465722
SEMA6B	ENST00000676793.1	c.2551A>T	p.Ser851Cys	missense_variant	17/17			ENSP00000503414	P1
SEMA6B	ENST00000677828.1	c.*1813A>T		3_prime_UTR_variant, NMD_transcript_variant	17/17			ENSP00000503277

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2021

The c.2551A>T (p.S851C) alteration is located in exon 17 (coding exon 16) of the SEMA6B gene. This alteration results from a A to T substitution at nucleotide position 2551, causing the serine (S) at amino acid position 851 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.028
Eigen_PC	Benign	0.070
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Pathogenic	0.95	D
Sift4G	Benign	0.064	T
Polyphen		0.98	D
Vest4		0.15
MutPred		0.21		Loss of glycosylation at S851 (P = 0.0071);
MVP		0.043
MPC		3.1
ClinPred		0.89	D
GERP RS		3.5
Varity_R		0.21
gMVP		0.34

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.

Other links and lift over

hg19: chr19-4543729;