22-40040969-G-C

Position:

• chr22-40040969-G-C

Variant summary

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

The ENST00000333407.11(FAM83F):​c.*11404G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,198 control chromosomes in the GnomAD database, including 3,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3405 hom., cov: 32)
  • Exomes 𝑓: 0.30 (2 hom.)
• Consequence: FAM83F ENST00000333407.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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 (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM83F	NM_138435.4	c.*11404G>C		3_prime_UTR_variant	5/5	ENST00000333407.11	NP_612444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM83F	ENST00000333407.11	c.*11404G>C		3_prime_UTR_variant	5/5	1	NM_138435.4	ENSP00000330432	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31263 AN: 152060 Hom.: 3405 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.300 AC: 6 AN: 20 Hom.: 2 Cov.: 0 AF XY: 0.222 AC XY: 4 AN XY: 18

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.206 AC: 31279 AN: 152178 Hom.: 3405 Cov.: 32 AF XY: 0.202 AC XY: 15028 AN XY: 74394

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.189

Alfa AF: 0.200 Hom.: 394

Bravo AF: 0.199

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.5
DANN	Benign	0.73

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: rs11704416; hg19: chr22-40436973;