Genetic Variant FAM120AOS:p.Thr248Ile (chr9-93447639-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP5BP4

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

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

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 VariationId is 183343.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

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

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
FAM120AOS	NM_198841.4	MANE Select	c.743C>T	p.Thr248Ile	missense	Exon 3 of 3	NP_942138.2
FAM120AOS	NM_001322224.3		c.197C>T	p.Thr66Ile	missense	Exon 3 of 3	NP_001309153.1
FAM120AOS	NR_136229.2		n.1042C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FAM120AOS	ENST00000375412.11	TSL:1 MANE Select	c.743C>T	p.Thr248Ile	missense	Exon 3 of 3	ENSP00000364561.5
FAM120AOS	ENST00000423591.5	TSL:1	c.197C>T	p.Thr66Ile	missense	Exon 3 of 3	ENSP00000414298.1
FAM120AOS	ENST00000476484.5	TSL:1	n.*141C>T		non_coding_transcript_exon	Exon 4 of 4	ENSP00000429212.1

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

GnomAD2 exomes

AF:

0.0000676

AC:

AN:

251426

AF XY:

0.0000809

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 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

African (AFR)

AF:

0.000448

AC:

AN:

33478

American (AMR)

AF:

0.000134

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111896

Other (OTH)

AF:

0.0000497

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

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

AF:

0.000250

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.000892

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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

ClinVar submissions as Germline

Significance:Likely pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

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 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.033

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0035

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.21

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.29

MVP

0.068

MPC

1.6

ClinPred

0.058

GERP RS

-2.3

Varity_R

0.21

gMVP

0.023

Mutation Taster

=28/72

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over