chr10-24543956-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019590.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	NM_019590.5	MANE Select	c.4686C>T	p.Thr1562Thr	synonymous	Exon 19 of 21	NP_062536.2
	KIAA1217	NM_001282767.2		c.3505-1025C>T		intron	N/A	NP_001269696.1
	KIAA1217	NM_001282768.2		c.3430-1025C>T		intron	N/A	NP_001269697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1217	ENST00000376454.8	TSL:1 MANE Select	c.4686C>T	p.Thr1562Thr	synonymous	Exon 19 of 21	ENSP00000365637.3
	KIAA1217	ENST00000376451.4	TSL:1	c.3735C>T	p.Thr1245Thr	synonymous	Exon 14 of 15	ENSP00000365634.2
	KIAA1217	ENST00000376452.7	TSL:1	c.3505-1025C>T		intron	N/A	ENSP00000365635.3

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

GnomAD2 exomes AF: 0.208 AC: 52220 AN: 251300 AF XY: 0.199

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 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

African (AFR) AF: 0.331 AC: 11075 AN: 33474

American (AMR) AF: 0.263 AC: 11759 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3255 AN: 26136

East Asian (EAS) AF: 0.391 AC: 15530 AN: 39700

South Asian (SAS) AF: 0.198 AC: 17067 AN: 86256

European-Finnish (FIN) AF: 0.205 AC: 10939 AN: 53388

Middle Eastern (MID) AF: 0.173 AC: 999 AN: 5766

European-Non Finnish (NFE) AF: 0.145 AC: 161113 AN: 1111950

Other (OTH) AF: 0.180 AC: 10879 AN: 60396

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

African (AFR) AF: 0.330 AC: 13671 AN: 41400

American (AMR) AF: 0.228 AC: 3488 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2076 AN: 5128

South Asian (SAS) AF: 0.218 AC: 1047 AN: 4796

European-Finnish (FIN) AF: 0.211 AC: 2225 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9761 AN: 67972

Other (OTH) AF: 0.198 AC: 418 AN: 2110

Alfa AF: 0.167 Hom.: 8379

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.027
DANN	Benign	0.54
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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