NM_019590.5:c.926C>A

Variant names:

• chr10-24473307-C-A
• rs771590028
• NM_019590.5:c.926C>A

Variant summary

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

The NM_019590.5(KIAA1217):​c.926C>A​(p.Ala309Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 1,403,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000043 (0 hom.)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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=0.1746327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.926C>A	p.Ala309Glu	missense_variant	Exon 6 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.926C>A	p.Ala309Glu	missense_variant	Exon 6 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000427 AC: 6 AN: 1403908 Hom.: 0 Cov.: 31 AF XY: 0.00000579 AC XY: 4 AN XY: 691328

Gnomad4 AFR exome AF: 0.0000940

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: 0.00000185

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.034	.;T;.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.94	.;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	.;.;M;M;.;M;.;.;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N;N;N;N;.;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.087	T;T;T;.;.;D;T;D;D;D;D
Sift4G	Benign	0.34	T;T;D;D;T;D;T;T;T;T;T
Polyphen		0.99, 1.0, 0.98, 0.99	.;.;D;.;.;D;.;D;D;D;D
Vest4		0.58
MutPred		0.072		.;Gain of solvent accessibility (P = 0.0421);Gain of solvent accessibility (P = 0.0421);Gain of solvent accessibility (P = 0.0421);.;Gain of solvent accessibility (P = 0.0421);.;.;.;.;.;
MVP		0.55
MPC		0.54
ClinPred		0.44	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.36

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: rs771590028; hg19: chr10-24762236;