rs1476530522

Variant names:

• chr5-116446678-C-A
• rs1476530522
• NM_020796.5:c.3028G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-116446678-C-A
• chr5-116446678-C-G
• chr5-116446678-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020796.5(SEMA6A):​c.3028G>T​(p.Val1010Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,782 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. V1010I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SEMA6A NM_020796.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38
• Publications: 0 publications found

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]

SEMA6A-AS1 (HGNC:51110): (SEMA6A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020796.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6A	NM_020796.5	MANE Select	c.3028G>T	p.Val1010Leu	missense	Exon 19 of 19	NP_065847.1	Q9H2E6-1
	SEMA6A	NM_001300780.2		c.3079G>T	p.Val1027Leu	missense	Exon 20 of 20	NP_001287709.1	Q9H2E6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6A	ENST00000343348.11	TSL:1 MANE Select	c.3028G>T	p.Val1010Leu	missense	Exon 19 of 19	ENSP00000345512.6	Q9H2E6-1
	SEMA6A	ENST00000257414.12	TSL:1	c.3079G>T	p.Val1027Leu	missense	Exon 20 of 20	ENSP00000257414.8	Q9H2E6-2
	SEMA6A	ENST00000510263.5	TSL:1	c.3028G>T	p.Val1010Leu	missense	Exon 19 of 19	ENSP00000424388.1	Q9H2E6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408782 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 694142

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32588

American (AMR) AF: 0.00 AC: 0 AN: 39140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23120

East Asian (EAS) AF: 0.00 AC: 0 AN: 38764

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083948

Other (OTH) AF: 0.00 AC: 0 AN: 58088

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.56	T
PhyloP100		7.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.16		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.73
MPC		0.77
ClinPred		0.96	D
GERP RS		4.4
gMVP		0.37
Mutation Taster		=14/86	disease causing

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

Other links and lift over

dbSNP: rs1476530522; hg19: chr5-115782374;