chr11-59109679-C-G

Variant names:

• chr11-59109679-C-G
• NM_198947.4:c.54C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198947.4(FAM111B):​c.54C>G​(p.Asp18Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: FAM111B NM_198947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.121602684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM111B	NM_198947.4	c.54C>G	p.Asp18Glu	missense_variant	Exon 3 of 4	ENST00000343597.4	NP_945185.1
FAM111B	NM_001142703.2	c.-10+967C>G		intron_variant	Intron 2 of 2		NP_001136175.1
FAM111B	NM_001142704.2	c.-10+2383C>G		intron_variant	Intron 1 of 1		NP_001136176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM111B	ENST00000343597.4	c.54C>G	p.Asp18Glu	missense_variant	Exon 3 of 4	1	NM_198947.4	ENSP00000341565.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459806 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.2
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.28	.;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.47	N;.
REVEL	Benign	0.075
Sift	Benign	0.12	T;.
Sift4G	Benign	0.53	T;T
Polyphen		0.94	P;P
Vest4		0.088
MutPred		0.084		Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.60
MPC		0.10
ClinPred		0.17	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.058
gMVP		0.024

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-58877152;