9-93452028-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_014612.5(FAM120A):​c.113G>A​(p.Arg38Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000512 in 1,562,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

FAM120A
NM_014612.5 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40
Variant links:
Genes affected
FAM120A (HGNC:13247): (family with sequence similarity 120 member A) Enables RNA binding activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]
FAM120AOS (HGNC:23389): (family with sequence similarity 120 member A opposite strand) Differences in the expression level of this gene are associated with the survival rate of those with glioma. [provided by RefSeq, May 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FAM120A. . Gene score misZ 3.3485 (greater than the threshold 3.09). Trascript score misZ 5.0695 (greater than threshold 3.09). GenCC has associacion of gene with Tourette syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.17479706).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FAM120ANM_014612.5 linkuse as main transcriptc.113G>A p.Arg38Gln missense_variant 1/18 ENST00000277165.11 NP_055427.2
FAM120AOSNM_198841.4 linkuse as main transcriptc.563+119C>T intron_variant ENST00000375412.11 NP_942138.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FAM120AENST00000277165.11 linkuse as main transcriptc.113G>A p.Arg38Gln missense_variant 1/181 NM_014612.5 ENSP00000277165 P3Q9NZB2-1
FAM120AOSENST00000375412.11 linkuse as main transcriptc.563+119C>T intron_variant 1 NM_198841.4 ENSP00000364561 P2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000284
AC:
4
AN:
1410896
Hom.:
0
Cov.:
34
AF XY:
0.00000143
AC XY:
1
AN XY:
697560
show subpopulations
Gnomad4 AFR exome
AF:
0.0000618
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000245
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152064
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ExAC
AF:
0.00000910
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2022The c.113G>A (p.R38Q) alteration is located in exon 1 (coding exon 1) of the FAM120A gene. This alteration results from a G to A substitution at nucleotide position 113, causing the arginine (R) at amino acid position 38 to be replaced by a glutamine (Q). 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
0.36
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.026
T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.51
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Pathogenic
0.82
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.41
N;N
MutationTaster
Benign
0.94
D;D;D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.16
N;N
REVEL
Benign
0.030
Sift
Benign
0.35
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.40
B;P
Vest4
0.050
MutPred
0.27
Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);
MVP
0.38
MPC
3.0
ClinPred
0.30
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.0
Varity_R
0.19
gMVP
0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756246014; hg19: chr9-96214310; API