rs147568761

Variant names:

• chr22-40019243-C-G
• rs147568761
• NM_138435.4:c.565C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-40019243-C-G
• chr22-40019243-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138435.4(FAM83F):​c.565C>G​(p.Arg189Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R189Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM83F NM_138435.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 0 publications found

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]

ACMG classification

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=0.15500543).

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.565C>G	p.Arg189Gly	missense	Exon 2 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.565C>G	p.Arg189Gly	missense	Exon 2 of 5	ENSP00000330432.5	Q8NEG4-1
	FAM83F	ENST00000473717.1	TSL:1	c.61C>G	p.Arg21Gly	missense	Exon 2 of 5	ENSP00000476600.1	Q8NEG4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.62
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.11
Sift	Benign	0.26	T
Sift4G	Benign	0.10	T
Polyphen		0.12	B
Vest4		0.37
MutPred		0.52		Loss of stability (P = 0.0437)
MVP		0.18
MPC		0.31
ClinPred		0.12	T
GERP RS		0.24
Varity_R		0.16
gMVP		0.55
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs147568761; hg19: chr22-40415247;