Variant chr6-73730401-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_133493.5(CD109):c.334G>A(p.Asp112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,614,052 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 3 hom. )

Consequence

CD109
NM_133493.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.993

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:

CD109 (HGNC:):

CD109 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009477615).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD109	NM_133493.5 linkuse as main transcript	c.334G>A	p.Asp112Asn	missense_variant	4/33	ENST00000287097.6	NP_598000.2	Q6YHK3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD109	ENST00000287097.6 linkuse as main transcript	c.334G>A	p.Asp112Asn	missense_variant	4/33	1	NM_133493.5	ENSP00000287097.4	Q6YHK3-1
CD109	ENST00000437994.6 linkuse as main transcript	c.334G>A	p.Asp112Asn	missense_variant	4/33	1		ENSP00000388062.2	Q6YHK3-4
CD109	ENST00000422508.6 linkuse as main transcript	c.277-5982G>A		intron_variant		1		ENSP00000404475.2	Q6YHK3-2
CD109	ENST00000649530.1 linkuse as main transcript	n.306G>A		non_coding_transcript_exon_variant	3/26

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

155

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000947

AC:

238

AN:

251354

Hom.:

AF XY:

0.000964

AC XY:

131

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00182

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00187

AC:

2727

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1277

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00233

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00102

AC:

155

AN:

152256

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00173

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00151

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.000964

AC:

117

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00130

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

Jan 26, 2022

The c.334G>A (p.D112N) alteration is located in exon 4 (coding exon 4) of the CD109 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the aspartic acid (D) at amino acid position 112 to be replaced by an asparagine (N). 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

0.070

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.010

.;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.0095

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.10

N;N

REVEL

Benign

0.084

Sift

Benign

0.56

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;B

Vest4

0.20

MVP

0.32

MPC

0.031

ClinPred

0.0012

GERP RS

2.0

Varity_R

0.018

gMVP

0.31

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

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