ENST00000376462.5:c.-54A>G

Variant names:

• chr10-24219742-A-G
• ENST00000376462.5:c.-54A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000376462.5(KIAA1217):​c.-54A>G variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1217 ENST00000376462.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• Publications: 0 publications found

Genes affected

KIAA1217 (HGNC:25428): (KIAA1217) Predicted to be involved in embryonic skeletal system development. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09814784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.187A>G	p.Ile63Val	missense_variant	Exon 2 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.187A>G	p.Ile63Val	missense_variant	Exon 2 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.187A>G (p.I63V) alteration is located in exon 2 (coding exon 2) of the KIAA1217 gene. This alteration results from a A to G substitution at nucleotide position 187, causing the isoleucine (I) at amino acid position 63 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0084	T;T;.;.;T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.098	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	.;.;N;N;N;.
PhyloP100		3.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.12	.;N;N;N;N;.
REVEL	Benign	0.075
Sift	Benign	0.55	.;T;T;.;T;.
Sift4G	Benign	1.0	.;T;T;T;T;T
Polyphen		0.10, 0.36	.;.;B;.;B;.
Vest4		0.31, 0.34, 0.41
MutPred		0.14		.;Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.48
MPC		0.51
ClinPred		0.39	T
GERP RS		4.6
Varity_R		0.053
gMVP		0.075
Mutation Taster		=81/19	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

hg19: chr10-24508671;