X-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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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;