dbSNP rs1013621621: FAM83F:p.Leu150Ile (chr22-39995490-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_138435.4(FAM83F):c.448C>A(p.Leu150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. L150F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FAM83F
NM_138435.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

0 publications found

Variant links:

Genes affected

FAM83F (HGNC:25148): (family with sequence similarity 83 member F) Predicted to enable protein kinase binding activity. Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

FAM83F 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=0.1085411).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138435.4. 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
	FAM83F	NM_138435.4	MANE Select	c.448C>A	p.Leu150Ile	missense	Exon 1 of 5	NP_612444.2	Q8NEG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83F	ENST00000333407.11	TSL:1 MANE Select	c.448C>A	p.Leu150Ile	missense	Exon 1 of 5	ENSP00000330432.5	Q8NEG4-1
	FAM83F	ENST00000488874.1	TSL:1	n.129C>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426610

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706478

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32638

American (AMR)

AF:

0.00

AC:

AN:

40670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25482

East Asian (EAS)

AF:

0.00

AC:

AN:

37602

South Asian (SAS)

AF:

0.00

AC:

AN:

81732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093990

Other (OTH)

AF:

0.00

AC:

AN:

58962

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.018

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.83

M_CAP

Benign

0.0099

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.10

PhyloP100

1.3

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.39

REVEL

Benign

0.057

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.45

Vest4

0.18

MutPred

0.46

Gain of MoRF binding (P = 0.1001)

MVP

0.33

MPC

0.28

ClinPred

0.52

GERP RS

3.9

Varity_R

0.21

gMVP

0.26

Mutation Taster

=91/9

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