5-94464974-T-C

Position:

• chr5-94464974-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145678.3(KIAA0825):​c.1958A>G​(p.Lys653Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA0825 NM_001145678.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0690

Genes affected

KIAA0825 (HGNC:28532): (KIAA0825)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046455592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA0825	NM_001145678.3	c.1958A>G	p.Lys653Arg	missense_variant	11/21	ENST00000682413.1	NP_001139150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA0825	ENST00000682413.1	c.1958A>G	p.Lys653Arg	missense_variant	11/21		NM_001145678.3	ENSP00000506760	A1
KIAA0825	ENST00000504117.1	n.805A>G		non_coding_transcript_exon_variant	5/9	1
KIAA0825	ENST00000703867.1	c.1958A>G	p.Lys653Arg	missense_variant	11/21			ENSP00000515512	P4
KIAA0825	ENST00000513200.7	c.1958A>G	p.Lys653Arg	missense_variant	10/20	5		ENSP00000424618	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1958A>G (p.K653R) alteration is located in exon 11 (coding exon 9) of the KIAA0825 gene. This alteration results from a A to G substitution at nucleotide position 1958, causing the lysine (K) at amino acid position 653 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.047
Sift	Benign	0.36	T
Sift4G	Benign	0.71	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.35		Loss of methylation at K653 (P = 0.0067);
MVP		0.048
ClinPred		0.12	T
GERP RS		-1.3
Varity_R		0.028

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: chr5-93800679;