5-116447178-A-G

Position:

• chr5-116447178-A-G

Variant summary

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

The NM_020796.5(SEMA6A):​c.2528T>C​(p.Leu843Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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)
• Consequence: SEMA6A NM_020796.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07

Genes affected

SEMA6A (HGNC:10738): (semaphorin 6A) Predicted to enable identical protein binding activity; signaling receptor binding activity; and transmembrane signaling receptor activity. Involved in cellular response to vascular endothelial growth factor stimulus; negative regulation of cell adhesion involved in sprouting angiogenesis; and negative regulation of signal transduction. Predicted to be integral component of membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18210188).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6A	NM_020796.5	c.2528T>C	p.Leu843Pro	missense_variant	19/19	ENST00000343348.11	NP_065847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6A	ENST00000343348.11	c.2528T>C	p.Leu843Pro	missense_variant	19/19	1	NM_020796.5	ENSP00000345512	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.2528T>C (p.L843P) alteration is located in exon 19 (coding exon 18) of the SEMA6A gene. This alteration results from a T to C substitution at nucleotide position 2528, causing the leucine (L) at amino acid position 843 to be replaced by a proline (P). 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	0.085
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0072	.;T;T;.;.
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	.;T;T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.90	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.15	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T
Polyphen		0.89, 0.76	.;.;P;P;.
Vest4		0.22
MutPred		0.37		Gain of disorder (P = 0.0089);.;.;.;Gain of disorder (P = 0.0089);
MVP		0.23
MPC		0.80
ClinPred		0.66	D
GERP RS		5.0
gMVP		0.52

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: chr5-115782874;