rs184467419

Variant names:

• chr11-59148707-C-G
• rs184467419
• ENST00000531147.1:c.-166C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-59148707-C-G
• chr11-59148707-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001312911.2(FAM111A):​c.-166C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 418,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: FAM111A NM_001312911.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• Publications: 0 publications found

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-DT (HGNC:53752): (FAM111A divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312911.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM111A	NM_001312909.2	MANE Select	c.-76-90C>G		intron	N/A	NP_001299838.1	Q96PZ2
	FAM111A	NM_001312911.2		c.-166C>G		5_prime_UTR	Exon 3 of 4	NP_001299840.1	Q96PZ2
	FAM111A	NM_001374849.1		c.-166C>G		5_prime_UTR	Exon 5 of 6	NP_001361778.1	Q96PZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM111A	ENST00000531147.1	TSL:1	c.-166C>G		5_prime_UTR	Exon 1 of 2	ENSP00000431631.1	Q96PZ2
	FAM111A	ENST00000675163.1	MANE Select	c.-76-90C>G		intron	N/A	ENSP00000501952.1	Q96PZ2
	FAM111A	ENST00000527629.6	TSL:3	c.-166C>G		5_prime_UTR	Exon 3 of 4	ENSP00000436128.2	Q96PZ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000239 AC: 1 AN: 418170 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 219854

African (AFR) AF: 0.00 AC: 0 AN: 11190

American (AMR) AF: 0.00 AC: 0 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12590

East Asian (EAS) AF: 0.00 AC: 0 AN: 28940

South Asian (SAS) AF: 0.00 AC: 0 AN: 36934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3202

European-Non Finnish (NFE) AF: 0.00000406 AC: 1 AN: 246058

Other (OTH) AF: 0.00 AC: 0 AN: 24166

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.13
DANN	Benign	0.59
PhyloP100		-0.15
PromoterAI		-0.0084	Neutral

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

Other links and lift over

dbSNP: rs184467419; hg19: chr11-58916180;