11-59148707-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001312911.2(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
NM_001312911.2 5_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.150
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 750 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM111ANM_001312909.2 linkc.-76-90C>T intron_variant Intron 4 of 5 ENST00000675163.1 NP_001299838.1 Q96PZ2A0A024R4Z3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM111AENST00000675163.1 linkc.-76-90C>T intron_variant Intron 4 of 5 NM_001312909.2 ENSP00000501952.1 Q96PZ2

Frequencies

GnomAD3 genomes
AF:
0.00493
AC:
750
AN:
152158
Hom.:
1
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 08, 2020
GeneDx
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

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

Other links and lift over

dbSNP: rs184467419; hg19: chr11-58916180; API