NM_020796.5:c.2909A>C

Variant names:

• chr5-116446797-T-G
• rs200578077
• NM_020796.5:c.2909A>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020796.5(SEMA6A):​c.2909A>C​(p.Gln970Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00573 in 1,613,124 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (31 hom.)
• Consequence: SEMA6A NM_020796.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.73
• Publications: 6 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007560551).
• BP6: Variant 5-116446797-T-G is Benign according to our data. Variant chr5-116446797-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 718147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 31 gene

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.2909A>C	p.Gln970Pro	missense	Exon 19 of 19	NP_065847.1	Q9H2E6-1
	SEMA6A	NM_001300780.2		c.2960A>C	p.Gln987Pro	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.2909A>C	p.Gln970Pro	missense	Exon 19 of 19	ENSP00000345512.6	Q9H2E6-1
	SEMA6A	ENST00000257414.12	TSL:1	c.2960A>C	p.Gln987Pro	missense	Exon 20 of 20	ENSP00000257414.8	Q9H2E6-2
	SEMA6A	ENST00000510263.5	TSL:1	c.2909A>C	p.Gln970Pro	missense	Exon 19 of 19	ENSP00000424388.1	Q9H2E6-1

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 640 AN: 152168 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00584

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00691

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00470 AC: 1159 AN: 246662 AF XY: 0.00464

Gnomad AFR exome AF: 0.00119

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00722

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00771

Gnomad NFE exome AF: 0.00720

Gnomad OTH exome AF: 0.00334

GnomAD4 exome AF: 0.00589 AC: 8600 AN: 1460838 Hom.: 31 Cov.: 31 AF XY: 0.00582 AC XY: 4231 AN XY: 726622

African (AFR) AF: 0.000747 AC: 25 AN: 33464

American (AMR) AF: 0.00159 AC: 71 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.00801 AC: 209 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39686

South Asian (SAS) AF: 0.000975 AC: 84 AN: 86144

European-Finnish (FIN) AF: 0.00786 AC: 419 AN: 53330

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00671 AC: 7458 AN: 1111452

Other (OTH) AF: 0.00545 AC: 329 AN: 60324

GnomAD4 genome AF: 0.00420 AC: 640 AN: 152286 Hom.: 1 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74460

African (AFR) AF: 0.00125 AC: 52 AN: 41568

American (AMR) AF: 0.00124 AC: 19 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00584 AC: 62 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00691 AC: 470 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00612 Hom.: 20

Bravo AF: 0.00379

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00908 AC: 35

ESP6500AA AF: 0.00120 AC: 5

ESP6500EA AF: 0.00733 AC: 62

ExAC AF: 0.00445 AC: 539

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0076	T
MetaSVM	Benign	-0.95	T
PhyloP100		5.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.23
Sift	Uncertain	0.012	D
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.59
MVP		0.41
MPC		0.71
ClinPred		0.026	T
GERP RS		4.3
gMVP		0.51
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs200578077; hg19: chr5-115782493; COSMIC: COSV99030636; COSMIC: COSV99030636;