rs534213077

Variant names:

• chr6-73730392-C-G
• NM_133493.5:c.325C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-73730392-C-G
• chr6-73730392-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133493.5(CD109):​c.325C>G​(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R109C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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]

ACMG classification

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=0.21508011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5	c.325C>G	p.Arg109Gly	missense_variant	Exon 4 of 33	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.325C>G	p.Arg109Gly	missense_variant	Exon 4 of 33	1	NM_133493.5	ENSP00000287097.4
CD109	ENST00000437994.6	c.325C>G	p.Arg109Gly	missense_variant	Exon 4 of 33	1		ENSP00000388062.2
CD109	ENST00000422508.6	c.277-5991C>G		intron_variant	Intron 3 of 31	1		ENSP00000404475.2
CD109	ENST00000649530.1	n.297C>G		non_coding_transcript_exon_variant	Exon 3 of 26

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727144

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.84
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.089
Sift	Benign	0.32	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0040	B;B
Vest4		0.54
MutPred		0.59		Gain of catalytic residue at D112 (P = 0.121);Gain of catalytic residue at D112 (P = 0.121);
MVP		0.13
MPC		0.039
ClinPred		0.11	T
GERP RS		1.2
Varity_R		0.10
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-74440115;