rs796051874

Positions:

• chr7-195685-T-A
• chr7-195685-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_020223.4(FAM20C):​c.737T>A​(p.Ile246Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.28

Genes affected

FAM20C (HGNC:22140): (FAM20C golgi associated secretory pathway kinase) This gene encodes a member of the family of secreted protein kinases. The encoded protein binds calcium and phosphorylates proteins involved in bone mineralization. Mutations in this gene are associated with the autosomal recessive disorder Raine syndrome. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929
• PP5: Variant 7-195685-T-A is Pathogenic according to our data. Variant chr7-195685-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 30876.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.737T>A	p.Ile246Asn	missense_variant	2/10	ENST00000313766.6	NP_064608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6	c.737T>A	p.Ile246Asn	missense_variant	2/10	1	NM_020223.4	ENSP00000322323	P1
FAM20C	ENST00000471328.1	n.61T>A		non_coding_transcript_exon_variant	1/2	3
FAM20C	ENST00000477004.1	n.218T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Lethal osteosclerotic bone dysplasia Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.094
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.068	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.82	P
Vest4		0.80
MutPred		0.64		Gain of disorder (P = 0.0031);
MVP		0.72
MPC		1.3
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.69
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs796051874; hg19: chr7-195685;