rs17506606

Positions:

• chr10-24380948-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019590.5(KIAA1217):​c.434C>G​(p.Ala145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,607,060 control chromosomes in the GnomAD database, including 43,771 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.17 (3039 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40732 hom.)
• Consequence: KIAA1217 NM_019590.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040133).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1217	NM_019590.5	c.434C>G	p.Ala145Gly	missense_variant	3/21	ENST00000376454.8	NP_062536.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1217	ENST00000376454.8	c.434C>G	p.Ala145Gly	missense_variant	3/21	1	NM_019590.5	ENSP00000365637	A2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26536 AN: 151994 Hom.: 3039 Cov.: 32

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.190 AC: 46884 AN: 247214 Hom.: 5622 AF XY: 0.198 AC XY: 26445 AN XY: 133772

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.0986

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.000718

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.228 AC: 331033 AN: 1454948 Hom.: 40732 Cov.: 32 AF XY: 0.228 AC XY: 164668 AN XY: 723566

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.000761

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.174 AC: 26526 AN: 152112 Hom.: 3039 Cov.: 32 AF XY: 0.171 AC XY: 12735 AN XY: 74354

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.173

Alfa AF: 0.236 Hom.: 3542

Bravo AF: 0.158

TwinsUK AF: 0.237 AC: 880

ALSPAC AF: 0.245 AC: 946

ESP6500AA AF: 0.0524 AC: 231

ESP6500EA AF: 0.260 AC: 2237

ExAC AF: 0.195 AC: 23712

Asia WGS AF: 0.0720 AC: 251 AN: 3478

EpiCase AF: 0.253

EpiControl AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	2.8
DANN	Benign	0.97
DEOGEN2	Benign	0.026	.;T;.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.67	.;T;T;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.49	.;.;N;N;.;N
MutationTaster	Benign	0.95	P;P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D;D;D;D;.;D
REVEL	Benign	0.18
Sift	Benign	0.35	T;T;T;.;.;T
Sift4G	Benign	0.31	T;T;T;T;T;T
Polyphen		0.0030, 0.0010	.;.;B;.;.;B
Vest4		0.025
MPC		0.12
ClinPred		0.014	T
GERP RS		-0.21
Varity_R		0.095
gMVP		0.11

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: rs17506606; hg19: chr10-24669877; COSMIC: COSV64605879;