X-54132719-C-T

Variant names:

• chrX-54132719-C-T
• NM_017848.6:c.2035G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017848.6(FAM120C):​c.2035G>A​(p.Ala679Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26460803).

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.2035G>A	p.Ala679Thr	missense	Exon 9 of 16	NP_060318.4
	FAM120C	NM_001300788.2		c.2035G>A	p.Ala679Thr	missense	Exon 9 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.2035G>A	p.Ala679Thr	missense	Exon 9 of 16	ENSP00000364324.2	Q9NX05-1
	FAM120C	ENST00000328235.4	TSL:1	c.2035G>A	p.Ala679Thr	missense	Exon 9 of 14	ENSP00000329896.4	F8W881

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Pathogenic	1.0
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.56	T
PhyloP100		4.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.24
MutPred		0.31		Gain of phosphorylation at A679 (P = 0.014)
MVP		0.45
MPC		1.7
ClinPred		0.93	D
GERP RS		4.8
gMVP		0.44
Mutation Taster		=50/50

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-54159152;