5-94386289-G-A

Variant names:

• chr5-94386289-G-A
• rs776944748
• NM_001145678.3:c.3572C>T

Variant summary

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

The NM_001145678.3(KIAA0825):​c.3572C>T​(p.Pro1191Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,399,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: KIAA0825 NM_001145678.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.96
• Publications: 1 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

ACMG classification

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

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.3572C>T	p.Pro1191Leu	missense	Exon 19 of 21	NP_001139150.1	A0A804HHT9
	KIAA0825	NM_001385712.1		c.3587C>T	p.Pro1196Leu	missense	Exon 20 of 22	NP_001372641.1	A0A994J718
	KIAA0825	NM_001388325.1		c.3587C>T	p.Pro1196Leu	missense	Exon 19 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.3572C>T	p.Pro1191Leu	missense	Exon 19 of 21	ENSP00000506760.1	A0A804HHT9
	KIAA0825	ENST00000703867.1		c.3587C>T	p.Pro1196Leu	missense	Exon 19 of 21	ENSP00000515512.1	A0A994J718
	KIAA0825	ENST00000513200.7	TSL:5	c.3572C>T	p.Pro1191Leu	missense	Exon 18 of 20	ENSP00000424618.2	Q8IV33-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000573 AC: 9 AN: 157028 AF XY: 0.0000842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 23 AN: 1399174 Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 18 AN XY: 690090

African (AFR) AF: 0.00 AC: 0 AN: 31584

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35698

South Asian (SAS) AF: 0.000290 AC: 23 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078800

Other (OTH) AF: 0.00 AC: 0 AN: 58008

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000400 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Polydactyly, postaxial, type a10 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.0
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.49		Loss of loop (P = 0.0112)
MVP		0.66
ClinPred		0.64	D
GERP RS		6.0
Varity_R		0.32
Mutation Taster		=72/28	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs776944748; hg19: chr5-93721994;