6-73758995-A-G

Variant summary

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

The NM_133493.5(CD109):c.725A>G(p.Asn242Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD109 NM_133493.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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=0.14091456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD109	NM_133493.5	c.725A>G	p.Asn242Ser	missense_variant	7/33	ENST00000287097.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD109	ENST00000287097.6	c.725A>G	p.Asn242Ser	missense_variant	7/33	1	NM_133493.5	P1
CD109	ENST00000437994.6	c.725A>G	p.Asn242Ser	missense_variant	7/33	1
CD109	ENST00000422508.6	c.494A>G	p.Asn165Ser	missense_variant	6/32	1
CD109	ENST00000649530.1	n.697A>G		non_coding_transcript_exon_variant	6/26

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

The c.725A>G (p.N242S) alteration is located in exon 7 (coding exon 7) of the CD109 gene. This alteration results from a A to G substitution at nucleotide position 725, causing the asparagine (N) at amino acid position 242 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	16
Dann	Uncertain	0.98
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.052
Sift	Benign	0.10	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.62	P;B;B
Vest4		0.32
MutPred		0.42		.;Gain of disorder (P = 0.0643);Gain of disorder (P = 0.0643);
MVP		0.23
MPC		0.028
ClinPred		0.17	T
GERP RS		2.7
Varity_R		0.036
gMVP		0.16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-74468718;