Genetic Variant FAM120AOS:p.Pro225Ala (chr9-93450490-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198841.4(FAM120AOS):c.673C>G(p.Pro225Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,419,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P225T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FAM120AOS
NM_198841.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.485

Publications

0 publications found

Variant links:

Genes affected

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09588936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198841.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM120AOS	NM_198841.4	MANE Select	c.673C>G	p.Pro225Ala	missense	Exon 2 of 3	NP_942138.2	Q5T036
FAM120AOS	NM_001322224.3		c.127C>G	p.Pro43Ala	missense	Exon 2 of 3	NP_001309153.1	E9PCY8
FAM120AOS	NR_136229.2		n.972C>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM120AOS	ENST00000375412.11	TSL:1 MANE Select	c.673C>G	p.Pro225Ala	missense	Exon 2 of 3	ENSP00000364561.5	Q5T036
FAM120AOS	ENST00000423591.5	TSL:1	c.127C>G	p.Pro43Ala	missense	Exon 2 of 3	ENSP00000414298.1	E9PCY8
FAM120AOS	ENST00000476484.5	TSL:1	n.127C>G		non_coding_transcript_exon	Exon 2 of 4	ENSP00000429212.1	E5RJ17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1419214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31124

American (AMR)

AF:

0.00

AC:

AN:

33972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23840

East Asian (EAS)

AF:

0.00

AC:

AN:

39244

South Asian (SAS)

AF:

0.00

AC:

AN:

80452

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094016

Other (OTH)

AF:

0.00

AC:

AN:

58414

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.2

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.030

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.55

M_CAP

Benign

0.0066

MetaRNN

Benign

0.096

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.48

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.092

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.12

MutPred

0.34

Loss of loop (P = 0.0022)

MVP

0.17

MPC

1.5

ClinPred

0.11

GERP RS

-1.2

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.0025

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over