X-54081388-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
FAM120CNM_017848.6 linkc.2912G>A p.Ser971Asn missense_variant Exon 14 of 16 ENST00000375180.7 NP_060318.4 Q9NX05-1
FAM120CNM_001300788.2 linkc.2500G>A p.Ala834Thr missense_variant Exon 12 of 14 NP_001287717.1 F8W881
FAM120CXM_006724589.5 linkc.*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
FAM120CENST00000375180.7 linkc.2912G>A p.Ser971Asn missense_variant Exon 14 of 16 1 NM_017848.6 ENSP00000364324.2 Q9NX05-1
FAM120CENST00000328235.4 linkc.2500G>A p.Ala834Thr missense_variant Exon 12 of 14 1 ENSP00000329896.4 F8W881

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
LINK: link

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; API