NM_020444.5:c.779C>G

Variant names:

• chr5-176347739-G-C
• rs1766635098
• NM_020444.5:c.779C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020444.5(KIAA1191):​c.779C>G​(p.Ala260Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1191 NM_020444.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.57
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32981607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1191	NM_020444.5	c.779C>G	p.Ala260Gly	missense_variant	Exon 9 of 9	ENST00000298569.9	NP_065177.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1191	ENST00000298569.9	c.779C>G	p.Ala260Gly	missense_variant	Exon 9 of 9	1	NM_020444.5	ENSP00000298569.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.779C>G (p.A260G) alteration is located in exon 9 (coding exon 7) of the KIAA1191 gene. This alteration results from a C to G substitution at nucleotide position 779, causing the alanine (A) at amino acid position 260 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;.;.;.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	.;.;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.7	M;.;.;.;M
PhyloP100		4.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D;D;.;.;D
REVEL	Benign	0.17
Sift	Benign	0.11	T;T;.;.;T
Sift4G	Benign	0.23	T;T;T;T;T
Polyphen		1.0	D;.;.;.;D
Vest4		0.37
MutPred		0.19		Loss of helix (P = 0.0237);.;.;.;Loss of helix (P = 0.0237);
MVP		0.56
MPC		0.66
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.27
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

dbSNP: rs1766635098; hg19: chr5-175774742;