rs1217748785

Variant names:

• chr5-116446711-C-G
• NM_020796.5:c.2995G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-116446711-C-G
• chr5-116446711-C-T

Variant summary

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

The NM_020796.5(SEMA6A):​c.2995G>C​(p.Gly999Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,443,196 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SEMA6A NM_020796.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6A	NM_020796.5	c.2995G>C	p.Gly999Arg	missense_variant	Exon 19 of 19	ENST00000343348.11	NP_065847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6A	ENST00000343348.11	c.2995G>C	p.Gly999Arg	missense_variant	Exon 19 of 19	1	NM_020796.5	ENSP00000345512.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1443196 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 715978

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	.;T;T;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	.;D;D;D;.
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-0.70	T
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;D
Polyphen		1.0	.;.;D;D;.
Vest4		0.80
MutPred		0.21		Gain of methylation at G999 (P = 0.0402);.;.;.;Gain of methylation at G999 (P = 0.0402);
MVP		0.54
MPC		0.85
ClinPred		0.99	D
GERP RS		4.4
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-115782407;