rs10455097

Variant names:

• chr6-73783709-A-C
• rs10455097
• NM_133493.5:c.2108A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133493.5(CD109):​c.2108A>C​(p.Tyr703Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,573,170 control chromosomes in the GnomAD database, including 209,847 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22741 hom., cov: 32)
  • Exomes 𝑓: 0.51 (187106 hom.)
• Consequence: CD109 NM_133493.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 54 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.0415844E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD109	NM_133493.5	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	Exon 19 of 33	ENST00000287097.6	NP_598000.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD109	ENST00000287097.6	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	Exon 19 of 33	1	NM_133493.5	ENSP00000287097.4
CD109	ENST00000437994.6	c.2108A>C	p.Tyr703Ser	missense_variant, splice_region_variant	Exon 19 of 33	1		ENSP00000388062.2
CD109	ENST00000422508.6	c.1877A>C	p.Tyr626Ser	missense_variant, splice_region_variant	Exon 18 of 32	1		ENSP00000404475.2
CD109	ENST00000649530.1	n.2080A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 18 of 26

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82155 AN: 151846 Hom.: 22719 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.531

GnomAD2 exomes AF: 0.512 AC: 127834 AN: 249794 AF XY: 0.502

Gnomad AFR exome AF: 0.649

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.523

Gnomad EAS exome AF: 0.518

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.504

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.511 AC: 725611 AN: 1421206 Hom.: 187106 Cov.: 24 AF XY: 0.508 AC XY: 360195 AN XY: 709484

African (AFR) AF: 0.653 AC: 21314 AN: 32616

American (AMR) AF: 0.592 AC: 26301 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 13563 AN: 25874

East Asian (EAS) AF: 0.517 AC: 20366 AN: 39416

South Asian (SAS) AF: 0.424 AC: 36101 AN: 85166

European-Finnish (FIN) AF: 0.438 AC: 23258 AN: 53110

Middle Eastern (MID) AF: 0.492 AC: 2798 AN: 5692

European-Non Finnish (NFE) AF: 0.513 AC: 551419 AN: 1075924

Other (OTH) AF: 0.517 AC: 30491 AN: 58964

GnomAD4 genome AF: 0.541 AC: 82220 AN: 151964 Hom.: 22741 Cov.: 32 AF XY: 0.534 AC XY: 39706 AN XY: 74300

African (AFR) AF: 0.655 AC: 27133 AN: 41454

American (AMR) AF: 0.534 AC: 8141 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1780 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2775 AN: 5172

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4814

European-Finnish (FIN) AF: 0.425 AC: 4482 AN: 10542

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34282 AN: 67948

Other (OTH) AF: 0.525 AC: 1108 AN: 2110

Alfa AF: 0.517 Hom.: 71819

Bravo AF: 0.560

TwinsUK AF: 0.514 AC: 1905

ALSPAC AF: 0.514 AC: 1982

ESP6500AA AF: 0.645 AC: 2841

ESP6500EA AF: 0.511 AC: 4395

ExAC AF: 0.509 AC: 61792

Asia WGS AF: 0.469 AC: 1629 AN: 3478

EpiCase AF: 0.513

EpiControl AF: 0.508

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.034
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.45
DEOGEN2	Benign	0.0029	.;.;T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.32	T;T;T
MetaRNN	Benign	0.0000040	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.8	.;N;N
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.9	N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.44	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.074
MPC		0.038
ClinPred		0.0030	T
GERP RS		5.2
Varity_R		0.063
gMVP		0.37
Mutation Taster		=96/4	polymorphism (auto)

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: rs10455097; hg19: chr6-74493432; COSMIC: COSV54646336;