10-24219649-G-C

Variant names:

• chr10-24219649-G-C
• NM_019590.5:c.94G>C
• KIAA1217 p.Val32Leu

Variant summary

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

The NM_019590.5(KIAA1217):​c.94G>C​(p.Val32Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V32I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50
• 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=0.11885217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019590.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	NM_019590.5	MANE Select	c.94G>C	p.Val32Leu	missense	Exon 2 of 21	NP_062536.2
	KIAA1217	NM_001282767.2		c.94G>C	p.Val32Leu	missense	Exon 2 of 19	NP_001269696.1	Q5T5P2-10
	KIAA1217	NM_001282768.2		c.94G>C	p.Val32Leu	missense	Exon 2 of 18	NP_001269697.1	Q5T5P2-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.94G>C	p.Val32Leu	missense	Exon 2 of 21	ENSP00000365637.3	Q5T5P2-1
	KIAA1217	ENST00000376452.7	TSL:1	c.94G>C	p.Val32Leu	missense	Exon 2 of 19	ENSP00000365635.3	Q5T5P2-10
	KIAA1217	ENST00000458595.5	TSL:1	c.94G>C	p.Val32Leu	missense	Exon 2 of 18	ENSP00000392625.1	Q5T5P2-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.071
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	L
PhyloP100		7.5
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	0.59	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.087
gMVP		0.19
Mutation Taster		=77/23	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-24508578;