11-59148707-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -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 VariationId is 1197694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 750 AD gene.

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>T		intron	N/A	NP_001299838.1	Q96PZ2
	FAM111A	NM_001312911.2		c.-166C>T		5_prime_UTR	Exon 3 of 4	NP_001299840.1	Q96PZ2
	FAM111A	NM_001374849.1		c.-166C>T		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>T		5_prime_UTR	Exon 1 of 2	ENSP00000431631.1	Q96PZ2
	FAM111A	ENST00000675163.1	MANE Select	c.-76-90C>T		intron	N/A	ENSP00000501952.1	Q96PZ2
	FAM111A	ENST00000527629.6	TSL:3	c.-166C>T		5_prime_UTR	Exon 3 of 4	ENSP00000436128.2	Q96PZ2

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152158 Hom.: 1 Cov.: 32

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

African (AFR) AF: 0.00107 AC: 12 AN: 11190

American (AMR) AF: 0.00468 AC: 71 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 13 AN: 12590

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

South Asian (SAS) AF: 0.00157 AC: 58 AN: 36934

European-Finnish (FIN) AF: 0.0131 AC: 522 AN: 39922

Middle Eastern (MID) AF: 0.00156 AC: 5 AN: 3202

European-Non Finnish (NFE) AF: 0.00639 AC: 1573 AN: 246042

Other (OTH) AF: 0.00401 AC: 97 AN: 24164

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152276 Hom.: 1 Cov.: 32 AF XY: 0.00540 AC XY: 402 AN XY: 74456

African (AFR) AF: 0.000770 AC: 32 AN: 41558

American (AMR) AF: 0.00654 AC: 100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4824

European-Finnish (FIN) AF: 0.0181 AC: 192 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00585 AC: 398 AN: 68022

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00335 Hom.: 1

Bravo AF: 0.00362

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.72
PhyloP100		-0.15
PromoterAI		-0.0086	Neutral
Mutation Taster		=100/0	polymorphism

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;