5-116447034-G-C

Variant names:

• chr5-116447034-G-C
• rs185504747
• NM_020796.5:c.2672C>G

Variant summary

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

The NM_020796.5(SEMA6A):​c.2672C>G​(p.Pro891Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P891L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SEMA6A NM_020796.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26

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.2672C>G	p.Pro891Arg	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.2672C>G	p.Pro891Arg	missense_variant	Exon 19 of 19	1	NM_020796.5	ENSP00000345512.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249014 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135200

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727126

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

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	Benign	0.19
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;T;.;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	.;D;D;D;.
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.50	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-4.4	D;D;D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	.;.;D;D;.
Vest4		0.79
MutPred		0.29		Gain of MoRF binding (P = 0.0071);.;.;.;Gain of MoRF binding (P = 0.0071);
MVP		0.36
MPC		0.58
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.56

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

Other links and lift over

dbSNP: rs185504747; hg19: chr5-115782730;