Variant 9-93452218-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The ENST00000277165.11(FAM120A):c.303G>T(p.Glu101Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,272 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FAM120A
ENST00000277165.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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]

FAM120A links:

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]

FAM120AOS links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.28842598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM120A	NM_014612.5 linkuse as main transcript	c.303G>T	p.Glu101Asp	missense_variant	1/18	ENST00000277165.11	NP_055427.2
FAM120AOS	NM_198841.4 linkuse as main transcript	c.492C>A	p.Phe164Leu	missense_variant	1/3	ENST00000375412.11	NP_942138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM120A	ENST00000277165.11 linkuse as main transcript	c.303G>T	p.Glu101Asp	missense_variant	1/18	1	NM_014612.5	ENSP00000277165	P3	Q9NZB2-1
FAM120AOS	ENST00000375412.11 linkuse as main transcript	c.492C>A	p.Phe164Leu	missense_variant	1/3	1	NM_198841.4	ENSP00000364561	P2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

240046

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459272

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725902

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.492C>A (p.F164L) alteration is located in exon 1 (coding exon 1) of the FAM120AOS gene. This alteration results from a C to A substitution at nucleotide position 492, causing the phenylalanine (F) at amino acid position 164 to be replaced by a leucine (L). 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

0.33

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.29

T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.093

Sift

Benign

0.38

T;T

Sift4G

Benign

0.22

T;T

Polyphen

0.34

B;D

Vest4

0.23

MutPred

0.39

Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);

MVP

0.26

MPC

0.96

ClinPred

0.97

GERP RS

3.8

Varity_R

0.38

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over