chr6-73696252-C-T

Variant names:

• chr6-73696252-C-T
• rs749960538
• NM_133493.5:c.37C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_133493.5(CD109):​c.37C>T​(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,540,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.375
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049862146).

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.37C>T	p.Leu13Phe	missense	Exon 1 of 33	NP_598000.2	Q6YHK3-1
	CD109	NM_001159587.3		c.37C>T	p.Leu13Phe	missense	Exon 1 of 33	NP_001153059.1	Q6YHK3-4
	CD109	NM_001159588.3		c.37C>T	p.Leu13Phe	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.37C>T	p.Leu13Phe	missense	Exon 1 of 33	ENSP00000287097.4	Q6YHK3-1
	CD109	ENST00000437994.6	TSL:1	c.37C>T	p.Leu13Phe	missense	Exon 1 of 33	ENSP00000388062.2	Q6YHK3-4
	CD109	ENST00000422508.6	TSL:1	c.37C>T	p.Leu13Phe	missense	Exon 1 of 32	ENSP00000404475.2	Q6YHK3-2

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000289

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000143 AC: 2 AN: 139856 AF XY: 0.00

Gnomad AFR exome AF: 0.000317

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000576 AC: 8 AN: 1388832 Hom.: 0 Cov.: 31 AF XY: 0.00000583 AC XY: 4 AN XY: 686028

African (AFR) AF: 0.000162 AC: 5 AN: 30924

American (AMR) AF: 0.00 AC: 0 AN: 36112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25030

East Asian (EAS) AF: 0.00 AC: 0 AN: 35506

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5552

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080454

Other (OTH) AF: 0.0000173 AC: 1 AN: 57880

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74324

African (AFR) AF: 0.000289 AC: 12 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.00000986 AC: 1

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	0.078
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L
PhyloP100		-0.38
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.018
Sift	Benign	0.086	T
Sift4G	Uncertain	0.045	D
Polyphen		0.0030	B
Vest4		0.036
MVP		0.16
MPC		0.033
ClinPred		0.053	T
GERP RS		1.6
PromoterAI		0.038	Neutral
Varity_R		0.072
gMVP		0.38
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: rs749960538; hg19: chr6-74405975; COSMIC: COSV54645069; COSMIC: COSV54645069;