rs1553970289

Variant names:

• chr4-127643769-AT-A
• rs1553970289
• NM_015693.4:c.396delT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_015693.4(INTU):​c.396delT​(p.Asn132LysfsTer11) 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: 32)
• Consequence: INTU NM_015693.4 frameshift
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.705

Genes affected

INTU (HGNC:29239): (inturned planar cell polarity protein) Involved in embryonic digit morphogenesis; roof of mouth development; and tongue morphogenesis. Located in ciliary basal body and motile cilium. Implicated in asphyxiating thoracic dystrophy and orofaciodigital syndrome XVII. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-127643769-AT-A is Pathogenic according to our data. Variant chr4-127643769-AT-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 504484.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INTU	NM_015693.4	c.396delT	p.Asn132LysfsTer11	frameshift_variant	Exon 2 of 16	ENST00000335251.11	NP_056508.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INTU	ENST00000335251.11	c.396delT	p.Asn132LysfsTer11	frameshift_variant	Exon 2 of 16	1	NM_015693.4	ENSP00000334003.5
INTU	ENST00000503952.5	n.396delT		non_coding_transcript_exon_variant	Exon 2 of 17	1		ENSP00000421995.1
INTU	ENST00000504491.1	c.339delT	p.Asn113LysfsTer11	frameshift_variant	Exon 2 of 2	4		ENSP00000422550.1
INTU	ENST00000503626.5	n.396delT		non_coding_transcript_exon_variant	Exon 2 of 18	2		ENSP00000426287.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Mohr syndrome Pathogenic:1

May 09, 2016

University of Washington Center for Mendelian Genomics, University of Washington

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Orofaciodigital syndrome 17 Pathogenic:1

Mar 30, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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: rs1553970289; hg19: chr4-128564924;