NM_019590.5:c.880G>C

Variant names:

• chr10-24473261-G-C
• NM_019590.5:c.880G>C

Variant summary

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

The NM_019590.5(KIAA1217):​c.880G>C​(p.Gly294Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91
• 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 2 ACMG points.

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

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.880G>C	p.Gly294Arg	missense	Exon 6 of 21	NP_062536.2
	KIAA1217	NM_001282767.2		c.880G>C	p.Gly294Arg	missense	Exon 6 of 19	NP_001269696.1	Q5T5P2-10
	KIAA1217	NM_001282768.2		c.880G>C	p.Gly294Arg	missense	Exon 6 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.880G>C	p.Gly294Arg	missense	Exon 6 of 21	ENSP00000365637.3	Q5T5P2-1
	KIAA1217	ENST00000376451.4	TSL:1	c.34G>C	p.Gly12Arg	missense	Exon 2 of 15	ENSP00000365634.2	Q5T5P2-3
	KIAA1217	ENST00000376452.7	TSL:1	c.880G>C	p.Gly294Arg	missense	Exon 6 of 19	ENSP00000365635.3	Q5T5P2-10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.25
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.32		Gain of solvent accessibility (P = 0.0012)
MVP		0.80
MPC		0.62
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.57
Mutation Taster		=79/21	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: chr10-24762190;