22-39995096-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_138435.4(FAM83F):c.54G>A(p.Val18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00713 in 1,356,248 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (57 hom.)
• Consequence: FAM83F NM_138435.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.430

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 22-39995096-G-A is Benign according to our data. Variant chr22-39995096-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.43 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM83F	NM_138435.4	c.54G>A	p.Val18=	synonymous_variant	1/5	ENST00000333407.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM83F	ENST00000333407.11	c.54G>A	p.Val18=	synonymous_variant	1/5	1	NM_138435.4	P1

Frequencies

GnomAD3 genomes AF: 0.00519 AC: 789 AN: 152012 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00521

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00786

Gnomad OTH AF: 0.00814

GnomAD3 exomes AF: 0.00510 AC: 41 AN: 8036 Hom.: 0 AF XY: 0.00486 AC XY: 22 AN XY: 4528

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00372

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00779

Gnomad OTH exome AF: 0.00431

GnomAD4 exome AF: 0.00738 AC: 8883 AN: 1204128 Hom.: 57 Cov.: 31 AF XY: 0.00728 AC XY: 4243 AN XY: 582476

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00435

Gnomad4 ASJ exome AF: 0.00308

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00338

Gnomad4 FIN exome AF: 0.00632

Gnomad4 NFE exome AF: 0.00814

Gnomad4 OTH exome AF: 0.00567

GnomAD4 genome AF: 0.00519 AC: 789 AN: 152120 Hom.: 2 Cov.: 32 AF XY: 0.00523 AC XY: 389 AN XY: 74354

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00521

Gnomad4 NFE AF: 0.00786

Gnomad4 OTH AF: 0.00806

Alfa AF: 0.00545 Hom.: 0

Bravo AF: 0.00484

Asia WGS AF: 0.00233 AC: 8 AN: 3450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

FAM83F: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	14
Dann	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs149259541; hg19: chr22-40391100;