rs7543148

Variant names:

• chr1-203348034-C-G
• rs7543148
• NM_002023.5:c.237G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-203348034-C-G
• chr1-203348034-C-T

Variant summary

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

The NM_002023.5(FMOD):​c.237G>C​(p.Glu79Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FMOD NM_002023.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.576
• Publications: 26 publications found

Genes affected

FMOD (HGNC:3774): (fibromodulin) Fibromodulin belongs to the family of small interstitial proteoglycans. The encoded protein possesses a central region containing leucine-rich repeats with 4 keratan sulfate chains, flanked by terminal domains containing disulphide bonds. Owing to the interaction with type I and type II collagen fibrils and in vitro inhibition of fibrillogenesis, the encoded protein may play a role in the assembly of extracellular matrix. It may also regulate TGF-beta activities by sequestering TGF-beta into the extracellular matrix. Sequence variations in this gene may be associated with the pathogenesis of high myopia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMOD	NM_002023.5	c.237G>C	p.Glu79Asp	missense_variant	Exon 2 of 3	ENST00000354955.5	NP_002014.2
FMOD	XM_047416304.1	c.237G>C	p.Glu79Asp	missense_variant	Exon 3 of 4		XP_047272260.1
FMOD	NR_103757.2	n.90+2999G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMOD	ENST00000354955.5	c.237G>C	p.Glu79Asp	missense_variant	Exon 2 of 3	1	NM_002023.5	ENSP00000347041.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 67

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	0.096
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.080	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.58
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.53
MutPred		0.40		Gain of loop (P = 0.0502);
MVP		0.93
MPC		0.33
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.63
gMVP		0.36
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7543148; hg19: chr1-203317162;