11-59148565-A-G

Position:

• chr11-59148565-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000531147(FAM111A):​c.-308A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 294,648 control chromosomes in the GnomAD database, including 7,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4431 hom., cov: 33)
  • Exomes 𝑓: 0.21 (3507 hom.)
• Consequence: FAM111A ENST00000531147 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.52

Genes affected

FAM111A (HGNC:24725): (FAM111 trypsin like peptidase A) The protein encoded by this gene is cell-cycle regulated, and has nuclear localization. The C-terminal half of the protein shares homology with trypsin-like peptidases and it contains a PCNA-interacting peptide (PIP) box, that is necessary for its co-localization with proliferating cell nuclear antigen (PCNA). Reduced expression of this gene resulted in DNA replication defects, consistent with the demonstrated role for this gene in Simian Virus 40 (SV40) viral replication. Mutations in this gene have been associated with Kenny-Caffey syndrome (KCS) type 2 and the more severe osteocraniostenosis (OCS, also known as Gracile Bone Dysplasia), both characterized by short stature, hypoparathyroidism, bone development abnormalities, and hypocalcemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

FAM111A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 11-59148565-A-G is Benign according to our data. Variant chr11-59148565-A-G is described in ClinVar as [Benign]. Clinvar id is 1286531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM111A	NM_001312909.2	c.-76-232A>G		intron_variant		ENST00000675163.1	NP_001299838.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM111A	ENST00000675163.1	c.-76-232A>G		intron_variant			NM_001312909.2	ENSP00000501952.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36047 AN: 152080 Hom.: 4419 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.212 AC: 30150 AN: 142450 Hom.: 3507 Cov.: 0 AF XY: 0.211 AC XY: 15564 AN XY: 73742

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.231

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.237 AC: 36092 AN: 152198 Hom.: 4431 Cov.: 33 AF XY: 0.236 AC XY: 17542 AN XY: 74412

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.219

Alfa AF: 0.212 Hom.: 940

Bravo AF: 0.243

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.33
DANN	Benign	0.39

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: rs7933787; hg19: chr11-58916038;