Variant rs140119177 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_198841.4(FAM120AOS):c.743C>T(p.Thr248Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,764 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 Likely pathogenic (no stars).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FAM120AOS
NM_198841.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.213

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:

Genome browser will be placed here

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;

PP5

Variant 9-93447639-G-A is Pathogenic according to our data. Variant chr9-93447639-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183343.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-93447639-G-A is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.029301971). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM120AOS	NM_198841.4 linkuse as main transcript	c.743C>T	p.Thr248Ile	missense_variant	3/3	ENST00000375412.11	NP_942138.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM120AOS	ENST00000375412.11 linkuse as main transcript	c.743C>T	p.Thr248Ile	missense_variant	3/3	1	NM_198841.4	ENSP00000364561	P2

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000871

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251426

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000250

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.000892

Gnomad4 AMR

AF:

0.0000654

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

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Cutis laxa;C0026827:Hypotonia;C0036439:Scoliosis;C0746102:Chronic lung disease;C1845847:Coarse facial features;C2051831:Pectus excavatum;C4317146:Gastroesophageal reflux;CN228273:Hyperactive airways;CN228277:Bilateral undescended testicles

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.033

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.53

T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.0020

B;.;.

Vest4

0.29

MVP

0.068

MPC

1.6

ClinPred

0.058

GERP RS

-2.3

Varity_R

0.21

gMVP

0.023

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