rs1750643604

Variant names:

• chr5-94396289-TGTTAAAA-T
• rs1750643604
• NM_001145678.3:c.3101_3107delTTTTAAC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001145678.3(KIAA0825):​c.3101_3107delTTTTAAC​(p.Leu1034GlnfsTer15) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0825 NM_001145678.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.48

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Verdict is Pathogenic. Variant got 12 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 5-94396289-TGTTAAAA-T is Pathogenic according to our data. Variant chr5-94396289-TGTTAAAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 3629776.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.3101_3107delTTTTAAC	p.Leu1034GlnfsTer15	frameshift_variant	Exon 17 of 21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.3101_3107delTTTTAAC	p.Leu1034GlnfsTer15	frameshift_variant	Exon 17 of 21		NM_001145678.3	ENSP00000506760.1
KIAA0825	ENST00000703867.1	c.3116_3122delTTTTAAC	p.Leu1039GlnfsTer15	frameshift_variant	Exon 17 of 21			ENSP00000515512.1
KIAA0825	ENST00000513200.7	c.3101_3107delTTTTAAC	p.Leu1034GlnfsTer15	frameshift_variant	Exon 16 of 20	5		ENSP00000424618.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polydactyly, postaxial, type a10 Pathogenic:1

Nov 07, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: KIAA0825 c.3101_3107delTTTTAAC (p.Leu1034GlnfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 186746 control chromosomes. To our knowledge, no occurrence of c.3101_3107delTTTTAAC in individuals affected with Polydactyly, Postaxial, Type A10 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1750643604; hg19: chr5-93731994;