11-59151621-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001312909.2(FAM111A):c.82-129A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 690,288 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (465 hom., cov: 33)
  • Exomes 𝑓: 0.019 (502 hom.)
• Consequence: FAM111A NM_001312909.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.453

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 11-59151621-A-T is Benign according to our data. Variant chr11-59151621-A-T is described in ClinVar as [Benign]. Clinvar id is 1267115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM111A	NM_001312909.2	c.82-129A>T		intron_variant		ENST00000675163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM111A	ENST00000675163.1	c.82-129A>T		intron_variant			NM_001312909.2	P2

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7199 AN: 152186 Hom.: 461 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00303

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0195 AC: 10490 AN: 537984 Hom.: 502 AF XY: 0.0191 AC XY: 5458 AN XY: 285078

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00991

Gnomad4 ASJ exome AF: 0.00125

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.0339

Gnomad4 FIN exome AF: 0.00389

Gnomad4 NFE exome AF: 0.00352

Gnomad4 OTH exome AF: 0.0231

GnomAD4 genome AF: 0.0474 AC: 7216 AN: 152304 Hom.: 465 Cov.: 33 AF XY: 0.0474 AC XY: 3529 AN XY: 74480

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0375

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.00730 Hom.: 8

Bravo AF: 0.0521

Asia WGS AF: 0.0920 AC: 317 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	9.2
Dann	Benign	0.83

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: rs60883299; hg19: chr11-58919094; COSMIC: COSV64655044; COSMIC: COSV64655044;