10-24219769-C-T

Variant names:

• chr10-24219769-C-T
• rs754656050
• NM_019590.5:c.214C>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.214C>T​(p.Pro72Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P72A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• 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=0.23395026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.214C>T	p.Pro72Ser	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.214C>T	p.Pro72Ser	missense_variant	Exon 2 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461648 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727146

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111888

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.11	T;T;.;.;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.38
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	.;.;L;L;L;.
PhyloP100		2.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.5	.;N;N;N;N;.
REVEL	Benign	0.097
Sift	Uncertain	0.016	.;D;D;.;D;.
Sift4G	Benign	0.064	.;T;D;D;D;D
Polyphen		0.86, 0.36	.;.;P;.;B;.
Vest4		0.58, 0.58, 0.48
MutPred		0.24		.;Gain of catalytic residue at P72 (P = 0.0143);Gain of catalytic residue at P72 (P = 0.0143);Gain of catalytic residue at P72 (P = 0.0143);Gain of catalytic residue at P72 (P = 0.0143);Gain of catalytic residue at P72 (P = 0.0143);
MVP		0.66
MPC		0.16
ClinPred		0.37	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.048
gMVP		0.22
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs754656050; hg19: chr10-24508698; COSMIC: COSV64601592;