Genetic Variant NM_020796.5:c.2986A>T (chr5-116446720-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020796.5(SEMA6A):c.2986A>T(p.Thr996Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,600,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

SEMA6A
NM_020796.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11256477).

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.2986A>T	p.Thr996Ser	missense	Exon 19 of 19	NP_065847.1	Q9H2E6-1
	SEMA6A	NM_001300780.2		c.3037A>T	p.Thr1013Ser	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.2986A>T	p.Thr996Ser	missense	Exon 19 of 19	ENSP00000345512.6	Q9H2E6-1
SEMA6A	ENST00000257414.12	TSL:1	c.3037A>T	p.Thr1013Ser	missense	Exon 20 of 20	ENSP00000257414.8	Q9H2E6-2
SEMA6A	ENST00000510263.5	TSL:1	c.2986A>T	p.Thr996Ser	missense	Exon 19 of 19	ENSP00000424388.1	Q9H2E6-1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000132

AC:

AN:

227122

AF XY:

0.00000814

show subpopulations

Gnomad AFR exome

AF:

0.000220

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000829

AC:

AN:

1447934

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

718812

show subpopulations

African (AFR)

AF:

0.000300

AC:

AN:

33296

American (AMR)

AF:

0.00

AC:

AN:

42418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25652

East Asian (EAS)

AF:

0.00

AC:

AN:

39296

South Asian (SAS)

AF:

0.00

AC:

AN:

84240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104874

Other (OTH)

AF:

0.0000167

AC:

AN:

59874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000118

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.000410

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.0000566

Hom.:

Bravo

AF:

0.000178

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.010

Eigen

Benign

-0.050

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

M_CAP

Benign

0.0064

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

6.1

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.47

REVEL

Benign

0.088

Sift

Benign

0.45

Sift4G

Benign

0.30

Polyphen

0.0040

Vest4

0.081

MutPred

0.11

Gain of glycosylation at T996 (P = 0.1336)

MVP

0.27

MPC

0.18

ClinPred

0.11

GERP RS

4.4

gMVP

0.23

Mutation Taster

=59/41

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