5-94403650-C-A

Position:

• chr5-94403650-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145678.3(KIAA0825):​c.2806G>T​(p.Val936Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,399,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: KIAA0825 NM_001145678.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.0420

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1673634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.2806G>T	p.Val936Phe	missense_variant	16/21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.2806G>T	p.Val936Phe	missense_variant	16/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000703867.1	c.2821G>T	p.Val941Phe	missense_variant	16/21			ENSP00000515512	P4
KIAA0825	ENST00000513200.7	c.2806G>T	p.Val936Phe	missense_variant	15/20	5		ENSP00000424618	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000500 AC: 7 AN: 1399274 Hom.: 0 Cov.: 31 AF XY: 0.00000724 AC XY: 5 AN XY: 690158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000649

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

KIAA0825-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2023

The KIAA0825 c.2806G>T variant is predicted to result in the amino acid substitution p.Val936Phe. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.21	B
Vest4		0.53
MutPred		0.24		Loss of ubiquitination at K933 (P = 0.0821);
MVP		0.23
ClinPred		0.11	T
GERP RS		-0.29
Varity_R		0.15

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-93739355;