X-54081388-C-T

Variant names:

• chrX-54081388-C-T
• NM_017848.6:c.2912G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017848.6(FAM120C):​c.2912G>A​(p.Ser971Asn) 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. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: FAM120C NM_017848.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13919473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120C	NM_017848.6	c.2912G>A	p.Ser971Asn	missense_variant	Exon 14 of 16	ENST00000375180.7	NP_060318.4
FAM120C	NM_001300788.2	c.2500G>A	p.Ala834Thr	missense_variant	Exon 12 of 14		NP_001287717.1
FAM120C	XM_006724589.5	c.*92G>A		3_prime_UTR_variant	Exon 15 of 15		XP_006724652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM120C	ENST00000375180.7	c.2912G>A	p.Ser971Asn	missense_variant	Exon 14 of 16	1	NM_017848.6	ENSP00000364324.2
FAM120C	ENST00000328235.4	c.2500G>A	p.Ala834Thr	missense_variant	Exon 12 of 14	1		ENSP00000329896.4

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2912G>A (p.S971N) 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 2912, causing the serine (S) at amino acid position 971 to be replaced by an asparagine (N). 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	Benign	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	18
DANN	Benign	0.97
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.050
Sift	Benign	0.046	D
Sift4G	Benign	0.23	T
Polyphen		0.011	B
Vest4		0.36
MutPred		0.28		Gain of phosphorylation at A834 (P = 0.0229);
MVP		0.43
ClinPred		0.72	D
GERP RS		4.0

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-54107821;