10-24219649-G-T

Variant names:

• chr10-24219649-G-T
• NM_019590.5:c.94G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019590.5(KIAA1217):​c.94G>T​(p.Val32Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.114771545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.94G>T	p.Val32Leu	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.94G>T	p.Val32Leu	missense_variant	Exon 2 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455494 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.;.;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.071
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.0	.;.;L;L;L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.54	.;N;N;N;N;.
REVEL	Benign	0.11
Sift	Benign	1.0	.;T;T;.;T;.
Sift4G	Benign	0.59	.;T;T;T;T;T
Polyphen		0.0030, 0.0060	.;.;B;.;B;.
Vest4		0.37, 0.33, 0.33
MutPred		0.13		.;Loss of methylation at K27 (P = 0.0811);Loss of methylation at K27 (P = 0.0811);Loss of methylation at K27 (P = 0.0811);Loss of methylation at K27 (P = 0.0811);Loss of methylation at K27 (P = 0.0811);
MVP		0.57
MPC		0.51
ClinPred		0.57	D
GERP RS		5.9
Varity_R		0.087
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-24508578;