22-40021816-A-G

Variant names:

• chr22-40021816-A-G
• rs5995794
• NM_138435.4:c.1306A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 18 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83F	NM_138435.4	MANE Select	c.1306A>G	p.Arg436Gly	missense	Exon 4 of 5	NP_612444.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM83F	ENST00000333407.11	TSL:1 MANE Select	c.1306A>G	p.Arg436Gly	missense	Exon 4 of 5	ENSP00000330432.5
	FAM83F	ENST00000473717.1	TSL:1	c.802A>G	p.Arg268Gly	missense	Exon 4 of 5	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

GnomAD2 exomes AF: 0.260 AC: 63927 AN: 245906 AF XY: 0.273

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 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

African (AFR) AF: 0.291 AC: 9753 AN: 33462

American (AMR) AF: 0.131 AC: 5848 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 7847 AN: 26092

East Asian (EAS) AF: 0.0699 AC: 2773 AN: 39686

South Asian (SAS) AF: 0.418 AC: 36061 AN: 86220

European-Finnish (FIN) AF: 0.276 AC: 14435 AN: 52340

Middle Eastern (MID) AF: 0.259 AC: 1491 AN: 5756

European-Non Finnish (NFE) AF: 0.281 AC: 312424 AN: 1111542

Other (OTH) AF: 0.283 AC: 17096 AN: 60340

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

African (AFR) AF: 0.285 AC: 11841 AN: 41482

American (AMR) AF: 0.189 AC: 2895 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1046 AN: 3468

East Asian (EAS) AF: 0.0818 AC: 422 AN: 5156

South Asian (SAS) AF: 0.416 AC: 2000 AN: 4808

European-Finnish (FIN) AF: 0.283 AC: 3002 AN: 10592

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19076 AN: 67876

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.267 Hom.: 8035

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 v4.9

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
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.90	L
PhyloP100		3.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.084	T
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
Mutation Taster		=99/1	polymorphism (auto)

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