NM_001145678.3:c.2206_2208delACA

Variant names:

• chr5-94462424-ATGT-A
• rs771443192
• NM_001145678.3:c.2206_2208delACA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PM4_Supporting BP6

The NM_001145678.3(KIAA0825):​c.2206_2208delACA​(p.Thr736del) variant causes a conservative 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 conservative_inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.68
• Publications: 0 publications found

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

KIAA0825 Gene-Disease associations (from GenCC):

• polydactyly, postaxial, type a10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• postaxial polydactyly type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309437 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• 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 VariationId is 3045394.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145678.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0825	NM_001145678.3	MANE Select	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21	NP_001139150.1	A0A804HHT9
	KIAA0825	NM_001385712.1		c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 13 of 22	NP_001372641.1	A0A994J718
	KIAA0825	NM_001388325.1		c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21	NP_001375254.1	A0A994J718

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0825	ENST00000682413.1	MANE Select	c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21	ENSP00000506760.1	A0A804HHT9
	KIAA0825	ENST00000504117.1	TSL:1	n.1053_1055delACA		non_coding_transcript_exon	Exon 6 of 9
	KIAA0825	ENST00000703867.1		c.2206_2208delACA	p.Thr736del	conservative_inframe_deletion	Exon 12 of 21	ENSP00000515512.1	A0A994J718

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

GnomAD2 exomes AF: 0.000396 AC: 56 AN: 141388 AF XY: 0.000334

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 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

African (AFR) AF: 0.00 AC: 0 AN: 29352

American (AMR) AF: 0.0000619 AC: 2 AN: 32330

Ashkenazi Jewish (ASJ) AF: 0.00398 AC: 96 AN: 24096

East Asian (EAS) AF: 0.00 AC: 0 AN: 35050

South Asian (SAS) AF: 0.00 AC: 0 AN: 74068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5230

European-Non Finnish (NFE) AF: 0.000189 AC: 192 AN: 1016736

Other (OTH) AF: 0.000398 AC: 22 AN: 55334

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

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.000131 AC: 2 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 11 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67830

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000912 Hom.: 0

Bravo AF: 0.000219

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA0825-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=73/27	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs771443192; hg19: chr5-93798129;