11-59125385-CAA-AGG

Variant names:

• chr11-59125385-CAA-AGG
• NM_198947.4:c.1288_1290delCAAinsAGG
• FAM111B p.Gln430Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_198947.4(FAM111B):​c.1288_1290delCAAinsAGG​(p.Gln430Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q430P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM111B NM_198947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

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]

FAM111B Gene-Disease associations (from GenCC):

• hereditary sclerosing poikiloderma with tendon and pulmonary involvement

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198947.4. 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
	FAM111B	NM_198947.4	MANE Select	c.1288_1290delCAAinsAGG	p.Gln430Arg	missense	N/A	NP_945185.1	Q6SJ93-1
	FAM111B	NM_001142703.2		c.1198_1200delCAAinsAGG	p.Gln400Arg	missense	N/A	NP_001136175.1	Q6SJ93-2
	FAM111B	NM_001142704.2		c.1198_1200delCAAinsAGG	p.Gln400Arg	missense	N/A	NP_001136176.1	Q6SJ93-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM111B	ENST00000343597.4	TSL:1 MANE Select	c.1288_1290delCAAinsAGG	p.Gln430Arg	missense	N/A	ENSP00000341565.3	Q6SJ93-1
	FAM111B	ENST00000529618.5	TSL:1	c.1198_1200delCAAinsAGG	p.Gln400Arg	missense	N/A	ENSP00000432875.1	Q6SJ93-2
	FAM111B	ENST00000620384.1	TSL:2	c.1288_1290delCAAinsAGG	p.Gln430Arg	missense	N/A	ENSP00000483456.1	Q6SJ93-1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-58892858;