22-39995127-G-C

Variant names:

• chr22-39995127-G-C
• rs2067366606
• NM_138435.4:c.85G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_138435.4(FAM83F):​c.85G>C​(p.Glu29Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. E29K) 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: 9.15
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

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.85G>C	p.Glu29Gln	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.85G>C	p.Glu29Gln	missense	Exon 1 of 5	ENSP00000330432.5	Q8NEG4-1
	FAM83F	ENST00000488874.1	TSL:1	n.-235G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.79
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.81	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.34	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		9.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.94		Gain of MoRF binding (P = 0.05)
MVP		0.74
MPC		2.9
ClinPred		1.0	D
GERP RS		3.1
PromoterAI		-0.059	Neutral
Varity_R		0.68
gMVP		0.79
Mutation Taster		=65/35	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: rs2067366606; hg19: chr22-40391131;