5-94462424-ATGT-A

Position:

• chr5-94462424-ATGT-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PM4_Supporting BP6

The NM_001145678.3(KIAA0825):​c.2206_2208del​(p.Thr736del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000229 in 1,472,994 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: KIAA0825 NM_001145678.3 inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.68

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001145678.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 5-94462424-ATGT-A is Benign according to our data. Variant chr5-94462424-ATGT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3045394.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.2206_2208del	p.Thr736del	inframe_deletion	12/21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.2206_2208del	p.Thr736del	inframe_deletion	12/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000504117.1	n.1053_1055del		non_coding_transcript_exon_variant	6/9	1
KIAA0825	ENST00000513200.7	c.2206_2208del	p.Thr736del	inframe_deletion	11/20	5		ENSP00000424618	A1
KIAA0825	ENST00000703867.1	c.2206_2208del	p.Thr736del	inframe_deletion	12/21			ENSP00000515512	P4

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 151930 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000396 AC: 56 AN: 141388 Hom.: 1 AF XY: 0.000334 AC XY: 25 AN XY: 74818

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000482

Gnomad ASJ exome AF: 0.00517

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000250

Gnomad OTH exome AF: 0.000253

GnomAD4 exome AF: 0.000236 AC: 312 AN: 1321064 Hom.: 1 AF XY: 0.000214 AC XY: 140 AN XY: 654104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000619

Gnomad4 ASJ exome AF: 0.00398

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.000171 AC: 26 AN: 151930 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74200

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00318

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000912 Hom.: 0

Bravo AF: 0.000219

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

KIAA0825-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 04, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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: rs771443192; hg19: chr5-93798129;