10-24543956-C-T

Variant names:

• chr10-24543956-C-T
• rs3748218
• NM_019590.5:c.4686C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_019590.5(KIAA1217):​c.4686C>T​(p.Thr1562Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,613,730 control chromosomes in the GnomAD database, including 26,974 homozygotes. 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: 𝑓 0.22 (4299 hom., cov: 31)
  • Exomes 𝑓: 0.17 (22675 hom.)
• Consequence: KIAA1217 NM_019590.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.4686C>T	p.Thr1562Thr	synonymous_variant	Exon 19 of 21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.4686C>T	p.Thr1562Thr	synonymous_variant	Exon 19 of 21	1	NM_019590.5	ENSP00000365637.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33362 AN: 151822 Hom.: 4286 Cov.: 31

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.200

GnomAD3 exomes AF: 0.208 AC: 52220 AN: 251300 Hom.: 6468 AF XY: 0.199 AC XY: 27052 AN XY: 135844

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.272

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.429

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.166 AC: 242616 AN: 1461790 Hom.: 22675 Cov.: 35 AF XY: 0.165 AC XY: 120276 AN XY: 727198

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.391

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.205

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.220 AC: 33406 AN: 151940 Hom.: 4299 Cov.: 31 AF XY: 0.223 AC XY: 16565 AN XY: 74236

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.198

Alfa AF: 0.154 Hom.: 3405

Bravo AF: 0.228

Asia WGS AF: 0.312 AC: 1083 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.027
DANN	Benign	0.54

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: rs3748218; hg19: chr10-24832885; COSMIC: COSV56824991; COSMIC: COSV56824991;