chr5-176348343-T-A

Variant names:

• chr5-176348343-T-A
• NM_020444.5:c.473A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020444.5(KIAA1191):​c.473A>T​(p.Gln158Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q158H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: KIAA1191 NM_020444.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.59
• Publications: 0 publications found

Genes affected

KIAA1191 (HGNC:29209): (KIAA1191) Predicted to enable oxidoreductase activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000250909 (HGNC:41234):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1191	NM_020444.5	c.473A>T	p.Gln158Leu	missense_variant	Exon 7 of 9	ENST00000298569.9	NP_065177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1191	ENST00000298569.9	c.473A>T	p.Gln158Leu	missense_variant	Exon 7 of 9	1	NM_020444.5	ENSP00000298569.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473A>T (p.Q158L) alteration is located in exon 7 (coding exon 5) of the KIAA1191 gene. This alteration results from a A to T substitution at nucleotide position 473, causing the glutamine (Q) at amino acid position 158 to be replaced by a leucine (L). 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	0.22
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	.;.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.7	M;.;.;.;M
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D;D;.;.;D
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D;D;.;.;D
Sift4G	Uncertain	0.036	D;D;D;D;D
Polyphen		0.98	D;.;.;.;D
Vest4		0.69
MutPred		0.21		Loss of methylation at K154 (P = 0.0822);.;.;.;Loss of methylation at K154 (P = 0.0822);
MVP		0.64
MPC		0.75
ClinPred		0.97	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.29
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr5-175775346;