rs1205434

Positions:

• chr20-38241114-C-A

Variant summary

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

The NM_001029864.2(KIAA1755):​c.1017G>T​(p.Lys339Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,613,864 control chromosomes in the GnomAD database, including 81,431 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.28 (6315 hom., cov: 32)
  • Exomes 𝑓: 0.32 (75116 hom.)
• Consequence: KIAA1755 NM_001029864.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048562884).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIAA1755	NM_001029864.2	c.1017G>T	p.Lys339Asn	missense_variant	3/14	ENST00000279024.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIAA1755	ENST00000279024.9	c.1017G>T	p.Lys339Asn	missense_variant	3/14	5	NM_001029864.2	P2
KIAA1755	ENST00000496900.2	c.1017G>T	p.Lys339Asn	missense_variant	3/8	2		A2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42695 AN: 152026 Hom.: 6310 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.310

GnomAD3 exomes AF: 0.303 AC: 76074 AN: 251022 Hom.: 12211 AF XY: 0.314 AC XY: 42688 AN XY: 135738

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.400

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.370

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.340

GnomAD4 exome AF: 0.317 AC: 463815 AN: 1461720 Hom.: 75116 Cov.: 52 AF XY: 0.321 AC XY: 233245 AN XY: 727182

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.404

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.320

Gnomad4 OTH exome AF: 0.325

GnomAD4 genome AF: 0.281 AC: 42707 AN: 152144 Hom.: 6315 Cov.: 32 AF XY: 0.281 AC XY: 20870 AN XY: 74386

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.310

Alfa AF: 0.324 Hom.: 20614

Bravo AF: 0.270

TwinsUK AF: 0.333 AC: 1233

ALSPAC AF: 0.326 AC: 1258

ESP6500AA AF: 0.201 AC: 886

ESP6500EA AF: 0.331 AC: 2844

ExAC AF: 0.307 AC: 37222

Asia WGS AF: 0.303 AC: 1057 AN: 3478

EpiCase AF: 0.336

EpiControl AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.53	T;T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.99	P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.13
Sift	Uncertain	0.027	D;.
Sift4G	Benign	0.061	T;T
Polyphen		0.013	B;.
Vest4		0.089
MutPred		0.14		Loss of ubiquitination at K339 (P = 0.0027);Loss of ubiquitination at K339 (P = 0.0027);
MPC		0.21
ClinPred		0.013	T
GERP RS		3.1
Varity_R		0.18
gMVP		0.39

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: rs1205434; hg19: chr20-36869516; COSMIC: COSV54076550; COSMIC: COSV54076550;