Variant chr11-59151621-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.453

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
FAM111A	NM_001312909.2 linkuse as main transcript	c.82-129A>T		intron_variant		ENST00000675163.1	NP_001299838.1	Q96PZ2A0A024R4Z3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM111A	ENST00000675163.1 linkuse as main transcript	c.82-129A>T		intron_variant			NM_001312909.2	ENSP00000501952.1		Q96PZ2

Frequencies

GnomAD3 genomes

AF:

0.0473

AC:

7199

AN:

152186

Hom.:

461

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0474

AC XY:

3529

AN XY:

74480

show subpopulations

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.:

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 26, 2019

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over