X-54073241-C-T

Variant names:

• chrX-54073241-C-T
• rs782159445
• NM_017848.6:c.3083G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017848.6(FAM120C):​c.3083G>A​(p.Arg1028Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,213 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.06
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041731834).

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.3083G>A	p.Arg1028Gln	missense	Exon 16 of 16	NP_060318.4
	FAM120C	NM_001300788.2		c.2671G>A	p.Gly891Ser	missense	Exon 14 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.3083G>A	p.Arg1028Gln	missense	Exon 16 of 16	ENSP00000364324.2	Q9NX05-1
	FAM120C	ENST00000328235.4	TSL:1	c.2671G>A	p.Gly891Ser	missense	Exon 14 of 14	ENSP00000329896.4	F8W881

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095213 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 360691

African (AFR) AF: 0.00 AC: 0 AN: 26369

American (AMR) AF: 0.00 AC: 0 AN: 35153

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

East Asian (EAS) AF: 0.00 AC: 0 AN: 30122

South Asian (SAS) AF: 0.0000185 AC: 1 AN: 53947

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839727

Other (OTH) AF: 0.00 AC: 0 AN: 45970

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	Benign	0.066
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.96
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.1
PROVEAN	Benign	0.29	N
REVEL	Benign	0.012
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.13
MutPred		0.25		Gain of sheet (P = 0.0149)
MVP		0.082
ClinPred		0.14	T
GERP RS		-4.2
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

dbSNP: rs782159445; hg19: chrX-54099674;