chrX-54081437-C-G

Variant names:

• chrX-54081437-C-G
• NM_017848.6:c.2863G>C

Variant summary

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

The NM_017848.6(FAM120C):​c.2863G>C​(p.Gly955Arg) variant causes a missense change involving the alteration of a 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: 21)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53
• Publications: 0 publications found

Genes affected

FAM120C (HGNC:16949): (family with sequence similarity 120 member C) This gene encodes a potential transmembrane protein and lies in a region where mutations and deletions have been associated with intellectual disability and autism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017848.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120C	NM_017848.6	MANE Select	c.2863G>C	p.Gly955Arg	missense	Exon 14 of 16	NP_060318.4
	FAM120C	NM_001300788.2		c.2451G>C	p.Lys817Asn	missense	Exon 12 of 14	NP_001287717.1	F8W881

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM120C	ENST00000375180.7	TSL:1 MANE Select	c.2863G>C	p.Gly955Arg	missense	Exon 14 of 16	ENSP00000364324.2	Q9NX05-1
	FAM120C	ENST00000328235.4	TSL:1	c.2451G>C	p.Lys817Asn	missense	Exon 12 of 14	ENSP00000329896.4	F8W881

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 21

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.79	T
PhyloP100		7.5
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.80
MutPred		0.29		Gain of solvent accessibility (P = 0.0037)
MVP		0.61
MPC		1.9
ClinPred		1.0	D
GERP RS		4.8
gMVP		0.81
Mutation Taster		=46/54	disease causing

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

hg19: chrX-54107870;