X-54116764-G-A

Variant names:

• chrX-54116764-G-A
• rs782733716
• NM_017848.6:c.2093C>T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_017848.6(FAM120C):​c.2093C>T​(p.Ala698Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000364 in 1,097,836 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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)
  • Exomes 𝑓: 0.0000036 (0 hom. 2 hem.)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2864304).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120C	NM_017848.6	c.2093C>T	p.Ala698Val	missense_variant	Exon 10 of 16	ENST00000375180.7	NP_060318.4
FAM120C	NM_001300788.2	c.2093C>T	p.Ala698Val	missense_variant	Exon 10 of 14		NP_001287717.1
FAM120C	XM_006724589.5	c.2093C>T	p.Ala698Val	missense_variant	Exon 10 of 15		XP_006724652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120C	ENST00000375180.7	c.2093C>T	p.Ala698Val	missense_variant	Exon 10 of 16	1	NM_017848.6	ENSP00000364324.2
FAM120C	ENST00000328235.4	c.2093C>T	p.Ala698Val	missense_variant	Exon 10 of 14	1		ENSP00000329896.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097836 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 2 AN XY: 363204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2093C>T (p.A698V) alteration is located in exon 10 (coding exon 10) of the FAM120C gene. This alteration results from a C to T substitution at nucleotide position 2093, causing the alanine (A) at amino acid position 698 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	24
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.97	.;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.83	N;N
REVEL	Benign	0.071
Sift	Benign	0.41	T;T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.18	.;B
Vest4		0.45
MutPred		0.27		Gain of relative solvent accessibility (P = 0.0215);Gain of relative solvent accessibility (P = 0.0215);
MVP		0.50
MPC		1.6
ClinPred		0.92	D
GERP RS		4.6
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782733716; hg19: chrX-54143197;