rs886039851

chr11-59125357-AAAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_198947.4(FAM111B):c.1262_1264del(p.Lys421del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM111B NM_198947.4 inframe_deletion
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.458

Genes affected

FAM111B (HGNC:24200): (FAM111 trypsin like peptidase B) This gene encodes a protein with a trypsin-like cysteine/serine peptidase domain in the C-terminus. Mutations in this gene are associated with an autosomal dominant form of hereditary fibrosing poikiloderma (HFP). Affected individuals display mottled pigmentation, telangiectasia, epidermal atrophy, tendon contractures, and progressive pulmonary fibrosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. A paralog of this gene which also has a trypsin‐like peptidase domain, FAM111A, is located only 16 kb from this gene on human chromosome 11q12.1. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_198947.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM111B	NM_198947.4	c.1262_1264del	p.Lys421del	inframe_deletion	4/4	ENST00000343597.4
FAM111B	NM_001142703.2	c.1172_1174del	p.Lys391del	inframe_deletion	3/3
FAM111B	NM_001142704.2	c.1172_1174del	p.Lys391del	inframe_deletion	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM111B	ENST00000343597.4	c.1262_1264del	p.Lys421del	inframe_deletion	4/4	1	NM_198947.4	P2
FAM111B	ENST00000529618.5	c.1172_1174del	p.Lys391del	inframe_deletion	3/3	1		A2
FAM111B	ENST00000411426.1	c.1172_1174del	p.Lys391del	inframe_deletion	2/2	4		A2
FAM111B	ENST00000620384.1	c.1262_1264del	p.Lys421del	inframe_deletion	2/2	2		P2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Hereditary sclerosing poikiloderma with tendon and pulmonary involvement Other:1

not provided, no classification provided

literature only

GeneReviews

-

May be associated with less severe extracutaneous phenotype. Further studies are needed. -

Computational scores

Source: dbNSFP v4.3

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: rs886039851; hg19: chr11-58892830;