dbSNP rs766918271: FAM124B:p.Val175Leu (chr2-224401246-C-A) – 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_001122779.2(FAM124B):c.523G>T(p.Val175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V175M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM124B
NM_001122779.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.71

Publications

0 publications found

Variant links:

Genes affected

FAM124B (HGNC:26224): (family with sequence similarity 124 member B) Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM124B 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=0.14101306).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122779.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM124B	NM_001122779.2	MANE Select	c.523G>T	p.Val175Leu	missense	Exon 1 of 2	NP_001116251.1	Q9H5Z6-1
	FAM124B	NM_024785.3		c.523G>T	p.Val175Leu	missense	Exon 1 of 3	NP_079061.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM124B	ENST00000409685.4	TSL:2 MANE Select	c.523G>T	p.Val175Leu	missense	Exon 1 of 2	ENSP00000386895.3	Q9H5Z6-1
FAM124B	ENST00000243806.2	TSL:1	c.523G>T	p.Val175Leu	missense	Exon 1 of 2	ENSP00000243806.2	Q9H5Z6-2
FAM124B	ENST00000389874.3	TSL:1	c.523G>T	p.Val175Leu	missense	Exon 1 of 3	ENSP00000374524.3	Q9H5Z6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

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:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

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:

60394

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.43

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.3

PhyloP100

1.7

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.9

REVEL

Benign

0.088

Sift

Benign

0.24

Sift4G

Benign

0.20

Polyphen

0.0080

Vest4

0.12

MutPred

0.25

Gain of ubiquitination at K180 (P = 0.1317)

MVP

0.41

MPC

0.17

ClinPred

0.85

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.26

Mutation Taster

=82/18

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over