rs149943652

Variant names:

• chr11-59152496-A-G
• rs149943652
• NM_001312909.2:c.828A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001312909.2(FAM111A):​c.828A>G​(p.Ala276Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,614,138 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FAM111A NM_001312909.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.13
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-59152496-A-G is Benign according to our data. Variant chr11-59152496-A-G is described in ClinVar as Benign. ClinVar VariationId is 435118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.
• BS2: High AC in GnomAd4 at 203 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001312909.2. 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.828A>G	p.Ala276Ala	synonymous	Exon 6 of 6	NP_001299838.1	Q96PZ2
	FAM111A	NM_001142519.3		c.828A>G	p.Ala276Ala	synonymous	Exon 5 of 5	NP_001135991.1	Q96PZ2
	FAM111A	NM_001142520.3		c.828A>G	p.Ala276Ala	synonymous	Exon 5 of 5	NP_001135992.1	Q96PZ2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM111A	ENST00000675163.1	MANE Select	c.828A>G	p.Ala276Ala	synonymous	Exon 6 of 6	ENSP00000501952.1	Q96PZ2
	FAM111A	ENST00000531147.1	TSL:1	c.828A>G	p.Ala276Ala	synonymous	Exon 2 of 2	ENSP00000431631.1	Q96PZ2
	FAM111A	ENST00000361723.7	TSL:2	c.828A>G	p.Ala276Ala	synonymous	Exon 4 of 4	ENSP00000355264.3	Q96PZ2

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00451

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000311 AC: 78 AN: 250566 AF XY: 0.000266

Gnomad AFR exome AF: 0.00390

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1461798 Hom.: 0 Cov.: 33 AF XY: 0.0000935 AC XY: 68 AN XY: 727186

African (AFR) AF: 0.00412 AC: 138 AN: 33474

American (AMR) AF: 0.000291 AC: 13 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111990

Other (OTH) AF: 0.000132 AC: 8 AN: 60394

GnomAD4 genome AF: 0.00133 AC: 203 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.00107 AC XY: 80 AN XY: 74504

African (AFR) AF: 0.00467 AC: 194 AN: 41578

American (AMR) AF: 0.000457 AC: 7 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00131 Hom.: 0

Bravo AF: 0.00148

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FAM111A-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.55
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149943652; hg19: chr11-58919969;