chrX-54081338-C-T

Variant names:

• chrX-54081338-C-T
• NM_017848.6:c.2962G>A

Variant summary

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

The NM_017848.6(FAM120C):​c.2962G>A​(p.Gly988Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,096,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.48

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 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 rank	MANE	Protein	UniProt
FAM120C	NM_017848.6	c.2962G>A	p.Gly988Ser	missense_variant	Exon 14 of 16	ENST00000375180.7	NP_060318.4
FAM120C	NM_001300788.2	c.2550G>A	p.Ser850Ser	synonymous_variant	Exon 12 of 14		NP_001287717.1
FAM120C	XM_006724589.5	c.*142G>A		downstream_gene_variant			XP_006724652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120C	ENST00000375180.7	c.2962G>A	p.Gly988Ser	missense_variant	Exon 14 of 16	1	NM_017848.6	ENSP00000364324.2
FAM120C	ENST00000328235.4	c.2550G>A	p.Ser850Ser	synonymous_variant	Exon 12 of 14	1		ENSP00000329896.4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096667 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 362177

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2962G>A (p.G988S) alteration is located in exon 14 (coding exon 14) of the FAM120C gene. This alteration results from a G to A substitution at nucleotide position 2962, causing the glycine (G) at amino acid position 988 to be replaced by a serine (S). 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	0.42
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.72	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.70
MutPred		0.29		Gain of glycosylation at G988 (P = 0.01);
MVP		0.40
MPC		1.7
ClinPred		1.0	D
GERP RS		4.0
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chrX-54107771; COSMIC: COSV60258159;