rs185504747

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_020796.5(SEMA6A):c.2672C>T(p.Pro891Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000361 in 1,613,868 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P891Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 4 hom. )

Consequence

SEMA6A
NM_020796.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.26

Publications

5 publications found

Variant links:

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 links:

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

SEMA6A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.100030005).

BP6

Variant 5-116447034-G-A is Benign according to our data. Variant chr5-116447034-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 713698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 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.2672C>T	p.Pro891Leu	missense	Exon 19 of 19	NP_065847.1	Q9H2E6-1
	SEMA6A	NM_001300780.2		c.2723C>T	p.Pro908Leu	missense	Exon 20 of 20	NP_001287709.1	Q9H2E6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA6A	ENST00000343348.11	TSL:1 MANE Select	c.2672C>T	p.Pro891Leu	missense	Exon 19 of 19	ENSP00000345512.6	Q9H2E6-1
SEMA6A	ENST00000257414.12	TSL:1	c.2723C>T	p.Pro908Leu	missense	Exon 20 of 20	ENSP00000257414.8	Q9H2E6-2
SEMA6A	ENST00000510263.5	TSL:1	c.2672C>T	p.Pro891Leu	missense	Exon 19 of 19	ENSP00000424388.1	Q9H2E6-1

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000454

AC:

113

AN:

249014

AF XY:

0.000518

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000550

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000443

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.000363

AC:

530

AN:

1461694

Hom.:

Cov.:

AF XY:

0.000385

AC XY:

280

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000537

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000371

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000330

AC:

367

AN:

1111862

Other (OTH)

AF:

0.000613

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000342

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41542

American (AMR)

AF:

0.000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5134

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

67972

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000855

AC:

ExAC

AF:

0.000439

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.091

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.054

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.50

PhyloP100

6.3

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.25

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.67

MVP

0.33

MPC

0.37

ClinPred

0.10

GERP RS

4.8

gMVP

0.54

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over