10-24380962-G-T

Variant names:

• chr10-24380962-G-T
• rs757517187
• NM_019590.5:c.448G>T

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.448G>T​(p.Ala150Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. A150T) has been classified as Uncertain significance.

• 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: 4.51
• 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=0.19216353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.448G>T	p.Ala150Ser	missense_variant	Exon 3 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.448G>T	p.Ala150Ser	missense_variant	Exon 3 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456776 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724652

African (AFR) AF: 0.0000300 AC: 1 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 43974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39430

South Asian (SAS) AF: 0.00 AC: 0 AN: 85572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109278

Other (OTH) AF: 0.00 AC: 0 AN: 60138

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;.;.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	.;T;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.81	.;.;L;L;.;L
PhyloP100		4.5
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.38	N;N;N;N;.;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T;T;.;.;T
Sift4G	Benign	0.19	T;D;D;D;T;D
Polyphen		0.98, 0.97	.;.;D;.;.;D
Vest4		0.47
MutPred		0.079		.;Gain of phosphorylation at A150 (P = 0.0061);Gain of phosphorylation at A150 (P = 0.0061);Gain of phosphorylation at A150 (P = 0.0061);.;Gain of phosphorylation at A150 (P = 0.0061);
MVP		0.63
MPC		0.54
ClinPred		0.67	D
GERP RS		5.5
Varity_R		0.058
gMVP		0.18
Mutation Taster		=92/8	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

dbSNP: rs757517187; hg19: chr10-24669891;