22-40021816-A-G

Position:

• chr22-40021816-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138435.4(FAM83F):​c.1306A>G​(p.Arg436Gly) variant causes a missense change. The variant allele was found at a frequency of 0.278 in 1,612,096 control chromosomes in the GnomAD database, including 65,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.27 (5823 hom., cov: 32)
  • Exomes 𝑓: 0.28 (59760 hom.)
• Consequence: FAM83F NM_138435.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004034877).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83F	NM_138435.4	c.1306A>G	p.Arg436Gly	missense_variant	4/5	ENST00000333407.11	NP_612444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83F	ENST00000333407.11	c.1306A>G	p.Arg436Gly	missense_variant	4/5	1	NM_138435.4	ENSP00000330432.5
FAM83F	ENST00000473717.1	c.802A>G	p.Arg268Gly	missense_variant	4/5	1		ENSP00000476600.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41131 AN: 151864 Hom.: 5825 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.260 AC: 63927 AN: 245906 Hom.: 9551 AF XY: 0.273 AC XY: 36584 AN XY: 134162

Gnomad AFR exome AF: 0.286

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.0841

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.277

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.279 AC: 407728 AN: 1460114 Hom.: 59760 Cov.: 38 AF XY: 0.284 AC XY: 206161 AN XY: 726346

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.0699

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.281

Gnomad4 OTH exome AF: 0.283

GnomAD4 genome AF: 0.271 AC: 41140 AN: 151982 Hom.: 5823 Cov.: 32 AF XY: 0.268 AC XY: 19941 AN XY: 74316

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.0818

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.281

Gnomad4 OTH AF: 0.269

Alfa AF: 0.265 Hom.: 5124

Bravo AF: 0.258

TwinsUK AF: 0.270 AC: 1003

ALSPAC AF: 0.276 AC: 1063

ESP6500AA AF: 0.271 AC: 1193

ESP6500EA AF: 0.280 AC: 2403

ExAC AF: 0.261 AC: 31501

Asia WGS AF: 0.270 AC: 937 AN: 3474

EpiCase AF: 0.289

EpiControl AF: 0.279

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.49	T;T
MetaRNN	Benign	0.0040	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N;.
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D;.
Sift4G	Benign	0.084	T;D
Polyphen		0.067	B;.
Vest4		0.16
MPC		0.34
ClinPred		0.028	T
GERP RS		2.7
Varity_R		0.096
gMVP		0.14

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

LitVar

Other links and lift over

dbSNP: rs5995794; hg19: chr22-40417820; COSMIC: COSV60999568;