chr7-193368-G-C

Position:

• chr7-193368-G-C

Variant summary

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

The NM_020223.4(FAM20C):​c.169G>C​(p.Ala57Pro) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM20C NM_020223.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0960

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]

(HGNC:):

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=0.13002485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20C	NM_020223.4	c.169G>C	p.Ala57Pro	missense_variant	1/10	ENST00000313766.6	NP_064608.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20C	ENST00000313766.6	c.169G>C	p.Ala57Pro	missense_variant	1/10	1	NM_020223.4	ENSP00000322323	P1
	ENST00000467050.1	n.233+580C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 15, 2022

This variant has not been reported in the literature in individuals affected with FAM20C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 57 of the FAM20C protein (p.Ala57Pro). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.093	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.78	T
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.14
Sift	Benign	0.12	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.36		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.13
MPC		0.89
ClinPred		0.11	T
GERP RS		3.1
Varity_R		0.16
gMVP		0.41

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: chr7-193368;