rs1938781

chr11-59147637-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001312909.2(FAM111A):c.-76-1160A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 151,976 control chromosomes in the GnomAD database, including 4,780 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (4780 hom., cov: 32)
• Consequence: FAM111A NM_001312909.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM111A	NM_001312909.2	c.-76-1160A>G		intron_variant		ENST00000675163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM111A	ENST00000675163.1	c.-76-1160A>G		intron_variant			NM_001312909.2	P2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37196 AN: 151860 Hom.: 4763 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.228

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.245 AC: 37252 AN: 151976 Hom.: 4780 Cov.: 32 AF XY: 0.243 AC XY: 18043 AN XY: 74270

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.225

Alfa AF: 0.214 Hom.: 1863

Bravo AF: 0.252

Asia WGS AF: 0.252 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.86
Dann	Benign	0.48

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: rs1938781; hg19: chr11-58915110;