rs730882244

Positions:

• chr14-35077175-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_173607.5(FAM177A1):​c.366dup​(p.Trp123MetfsTer16) variant causes a frameshift 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 Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM177A1 NM_173607.5 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.355

Genes affected

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-35077175-T-TA is Pathogenic according to our data. Variant chr14-35077175-T-TA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183348.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM177A1	NM_173607.5	c.366dup	p.Trp123MetfsTer16	frameshift_variant	3/5	ENST00000280987.9	NP_775878.2
FAM177A1	NM_001079519.1	c.297dup	p.Trp100MetfsTer16	frameshift_variant	5/7		NP_001072987.1
FAM177A1	NM_001289022.3	c.297dup	p.Trp100MetfsTer16	frameshift_variant	4/6		NP_001275951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM177A1	ENST00000280987.9	c.366dup	p.Trp123MetfsTer16	frameshift_variant	3/5	1	NM_173607.5	ENSP00000280987	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Dolichocephaly;C2243051:Macrocephaly;C3714756:Intellectual disability;CN228310:Mild obesity Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 01, 2014

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs730882244; hg19: chr14-35546381;