6-73696229-C-A

Variant names:

• chr6-73696229-C-A
• rs1255697894
• NM_133493.5:c.14C>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.14C>A​(p.Pro5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000359 in 1,392,334 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.90
• 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=0.04246068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133493.5. 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
	CD109	NM_133493.5	MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 33	NP_598000.2	Q6YHK3-1
	CD109	NM_001159587.3		c.14C>A	p.Pro5Gln	missense	Exon 1 of 33	NP_001153059.1	Q6YHK3-4
	CD109	NM_001159588.3		c.14C>A	p.Pro5Gln	missense	Exon 1 of 32	NP_001153060.1	Q6YHK3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD109	ENST00000287097.6	TSL:1 MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 33	ENSP00000287097.4	Q6YHK3-1
	CD109	ENST00000437994.6	TSL:1	c.14C>A	p.Pro5Gln	missense	Exon 1 of 33	ENSP00000388062.2	Q6YHK3-4
	CD109	ENST00000422508.6	TSL:1	c.14C>A	p.Pro5Gln	missense	Exon 1 of 32	ENSP00000404475.2	Q6YHK3-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000359 AC: 5 AN: 1392334 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 687808

African (AFR) AF: 0.00 AC: 0 AN: 31240

American (AMR) AF: 0.00 AC: 0 AN: 36318

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35818

South Asian (SAS) AF: 0.00 AC: 0 AN: 79454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1081504

Other (OTH) AF: 0.0000172 AC: 1 AN: 58012

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.012
DANN	Benign	0.92
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.018
Sift	Benign	0.63	T
Sift4G	Benign	0.46	T
Polyphen		0.0020	B
Vest4		0.060
MutPred		0.22		Loss of loop (P = 0.0128)
MVP		0.092
MPC		0.030
ClinPred		0.057	T
GERP RS		-8.5
PromoterAI		0.047	Neutral
Varity_R		0.023
gMVP		0.42
Mutation Taster		=95/5	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: rs1255697894; hg19: chr6-74405952;