chr6-73696223-G-A

Variant names:

• chr6-73696223-G-A
• rs920184106
• NM_133493.5:c.8G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133493.5(CD109):​c.8G>A​(p.Gly3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,393,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

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-AS1 (HGNC:55765): (CD109 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058447212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5	c.8G>A	p.Gly3Asp	missense_variant	Exon 1 of 33	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.8G>A	p.Gly3Asp	missense_variant	Exon 1 of 33	1	NM_133493.5	ENSP00000287097.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1393282 Hom.: 0 Cov.: 31 AF XY: 0.00000436 AC XY: 3 AN XY: 688222

African (AFR) AF: 0.00 AC: 0 AN: 31348

American (AMR) AF: 0.00 AC: 0 AN: 36344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35866

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79474

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1081740

Other (OTH) AF: 0.00 AC: 0 AN: 58056

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0085	.;.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N;N;N
PhyloP100		1.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Benign	0.044
Sift	Benign	0.081	T;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.16
MutPred		0.29		Loss of catalytic residue at G3 (P = 0.0034);Loss of catalytic residue at G3 (P = 0.0034);Loss of catalytic residue at G3 (P = 0.0034);
MVP		0.26
MPC		0.036
ClinPred		0.070	T
GERP RS		1.4
PromoterAI		0.016	Neutral
Varity_R		0.059
gMVP		0.69
Mutation Taster		=90/10	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: rs920184106; hg19: chr6-74405946;