Variant 6-73762780-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_133493.5(CD109):c.895A>G(p.Met299Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,608,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CD109
NM_133493.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.433

Variant links:

Genes affected

CD109 (HGNC:21685): (CD109 molecule) This gene encodes a glycosyl phosphatidylinositol (GPI)-linked glycoprotein that localizes to the surface of platelets, activated T-cells, and endothelial cells. The protein binds to and negatively regulates signalling by transforming growth factor beta (TGF-beta). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

CD109 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10930306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5 linkuse as main transcript	c.895A>G	p.Met299Val	missense_variant	9/33	ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6 linkuse as main transcript	c.895A>G	p.Met299Val	missense_variant	9/33	1	NM_133493.5	P1	Q6YHK3-1
CD109	ENST00000437994.6 linkuse as main transcript	c.895A>G	p.Met299Val	missense_variant	9/33	1			Q6YHK3-4
CD109	ENST00000422508.6 linkuse as main transcript	c.664A>G	p.Met222Val	missense_variant	8/32	1			Q6YHK3-2
CD109	ENST00000649530.1 linkuse as main transcript	n.867A>G		non_coding_transcript_exon_variant	8/26

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1456348

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.895A>G (p.M299V) alteration is located in exon 9 (coding exon 9) of the CD109 gene. This alteration results from a A to G substitution at nucleotide position 895, causing the methionine (M) at amino acid position 299 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.064

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.67

D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.23

T;D;D

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.24

MutPred

0.31

.;Gain of catalytic residue at M299 (P = 0.0434);Gain of catalytic residue at M299 (P = 0.0434);

MVP

0.23

MPC

0.031

ClinPred

0.17

GERP RS

4.9

Varity_R

0.10

gMVP

0.57

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over