11-59148707-C-T

Position:

• chr11-59148707-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000531147.1(FAM111A):​c.-166C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00544 in 570,422 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (9 hom.)
• Consequence: FAM111A ENST00000531147.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-59148707-C-T is Benign according to our data. Variant chr11-59148707-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1197694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00493 (750/152276) while in subpopulation AMR AF= 0.00654 (100/15292). AF 95% confidence interval is 0.0055. There are 1 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 750 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM111A	NM_001312909.2	c.-76-90C>T		intron_variant		ENST00000675163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM111A	ENST00000675163.1	c.-76-90C>T		intron_variant			NM_001312909.2	P2

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152158 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0181

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00585

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00562 AC: 2351 AN: 418146 Hom.: 9 Cov.: 3 AF XY: 0.00550 AC XY: 1209 AN XY: 219840

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.00468

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00157

Gnomad4 FIN exome AF: 0.0131

Gnomad4 NFE exome AF: 0.00639

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00540 AC XY: 402 AN XY: 74456

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0181

Gnomad4 NFE AF: 0.00585

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00335 Hom.: 1

Bravo AF: 0.00362

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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

GeneDx

Sep 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs184467419; hg19: chr11-58916180;