6-73730363-A-T

Variant names:

• chr6-73730363-A-T
• rs755160049
• NM_133493.5:c.296A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133493.5(CD109):​c.296A>T​(p.Asp99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 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. 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. D99G) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23376605).

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.296A>T	p.Asp99Val	missense	Exon 4 of 33	NP_598000.2	Q6YHK3-1
	CD109	NM_001159587.3		c.296A>T	p.Asp99Val	missense	Exon 4 of 33	NP_001153059.1	Q6YHK3-4
	CD109	NM_001159588.3		c.277-6020A>T		intron	N/A	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.296A>T	p.Asp99Val	missense	Exon 4 of 33	ENSP00000287097.4	Q6YHK3-1
	CD109	ENST00000437994.6	TSL:1	c.296A>T	p.Asp99Val	missense	Exon 4 of 33	ENSP00000388062.2	Q6YHK3-4
	CD109	ENST00000422508.6	TSL:1	c.277-6020A>T		intron	N/A	ENSP00000404475.2	Q6YHK3-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74344

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.76
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.1
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.0	B
Vest4		0.48
MutPred		0.51		Loss of phosphorylation at Y102 (P = 0.0595)
MVP		0.41
MPC		0.044
ClinPred		0.35	T
GERP RS		4.3
Varity_R		0.18
gMVP		0.50
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs755160049; hg19: chr6-74440086;