rs563441863

Variant names:

• chr10-24219658-C-A
• rs563441863
• NM_019590.5:c.103C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-24219658-C-A
• chr10-24219658-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019590.5(KIAA1217):​c.103C>A​(p.Pro35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: -0.355

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022846848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.103C>A	p.Pro35Thr	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.103C>A	p.Pro35Thr	missense_variant	Exon 2 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458408 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725184

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.5
DANN	Benign	0.56
DEOGEN2	Benign	0.0051	T;T;.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.023	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	.;.;N;N;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.44	.;N;N;N;N;.
REVEL	Benign	0.097
Sift	Benign	0.65	.;T;T;.;T;.
Sift4G	Benign	0.36	.;T;T;T;T;T
Polyphen		0.020, 0.010	.;.;B;.;B;.
Vest4		0.31, 0.29, 0.22
MutPred		0.093		.;Gain of phosphorylation at P35 (P = 0.0457);Gain of phosphorylation at P35 (P = 0.0457);Gain of phosphorylation at P35 (P = 0.0457);Gain of phosphorylation at P35 (P = 0.0457);Gain of phosphorylation at P35 (P = 0.0457);
MVP		0.21
MPC		0.13
ClinPred		0.075	T
GERP RS		-8.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs563441863; hg19: chr10-24508587;