Genetic Variant FAM120B:p.Ala159Pro (chr6-170317865-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_032448.3(FAM120B):c.475G>C(p.Ala159Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A159T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM120B
NM_032448.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.31

Publications

2 publications found

Variant links:

Genes affected

FAM120B (HGNC:21109): (family with sequence similarity 120 member B) Predicted to be involved in fat cell differentiation and peroxisome proliferator activated receptor signaling pathway. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM120B links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM120B	NM_032448.3 link	c.475G>C	p.Ala159Pro	missense_variant	Exon 2 of 11	ENST00000476287.4	NP_115824.1	Q96EK7-1B4DSS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM120B	ENST00000476287.4 link	c.475G>C	p.Ala159Pro	missense_variant	Exon 2 of 11	1	NM_032448.3	ENSP00000417970.1	Q96EK7-1
FAM120B	ENST00000537664.5 link	c.544G>C	p.Ala182Pro	missense_variant	Exon 2 of 11	2		ENSP00000440125.1	F5GY05
FAM120B	ENST00000630384.2 link	c.511G>C	p.Ala171Pro	missense_variant	Exon 2 of 11	2		ENSP00000485745.1	A0A0D9SEJ5
FAM120B	ENST00000625626.1 link	c.-90+11023G>C		intron_variant	Intron 1 of 8	2		ENSP00000485793.1	Q96EK7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251418

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

.;T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.83

D;D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.7

.;.;M

PhyloP100

9.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.3

.;D;D

REVEL

Uncertain

0.42

Sift

Benign

0.18

.;T;T

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.90

MutPred

0.53

.;.;Gain of disorder (P = 0.0666);

MVP

0.74

MPC

0.82

ClinPred

0.95

GERP RS

6.1

Varity_R

0.80

gMVP

0.96

Mutation Taster

=61/39

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over