17-68600373-G-T

Position:

• chr17-68600373-G-T

Variant summary

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

The NM_017565.4(FAM20A):​c.294C>A​(p.His98Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM20A NM_017565.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672

Genes affected

FAM20A (HGNC:23015): (FAM20A golgi associated secretory pathway pseudokinase) This locus encodes a protein that is likely secreted and may function in hematopoiesis. A mutation at this locus has been associated with amelogenesis imperfecta and gingival hyperplasia syndrome. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

LINC01482 (HGNC:51128): (long intergenic non-protein coding RNA 1482)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM20A	NM_017565.4	c.294C>A	p.His98Gln	missense_variant	1/11	ENST00000592554.2	NP_060035.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM20A	ENST00000592554.2	c.294C>A	p.His98Gln	missense_variant	1/11	1	NM_017565.4	ENSP00000468308.1
FAM20A	ENST00000590074.5	n.222C>A		non_coding_transcript_exon_variant	1/12	2		ENSP00000464910.1
LINC01482	ENST00000587999.1	n.198+2227G>T		intron_variant		3
LINC01482	ENST00000589610.5	n.40+8495G>T		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

GeneDx

Jul 09, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.083
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Pathogenic	0.89	D
Sift4G	Benign	0.068	T
Polyphen		0.95	P
Vest4		0.28
MutPred		0.52		Loss of catalytic residue at L100 (P = 0.0571);
MVP		0.57
MPC		0.55
ClinPred		0.90	D
GERP RS		1.4
Varity_R		0.88
gMVP		0.86

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: chr17-66596514;