rs1205434

Variant names:

• chr20-38241114-C-A
• rs1205434
• NM_001029864.2:c.1017G>T

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 27 publications found

Genes affected

KIAA1755 (HGNC:29372): (KIAA1755)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KIAA1755	NM_001029864.2	c.1017G>T	p.Lys339Asn	missense_variant	Exon 3 of 14	ENST00000279024.9	NP_001025035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1755	ENST00000279024.9	c.1017G>T	p.Lys339Asn	missense_variant	Exon 3 of 14	5	NM_001029864.2	ENSP00000279024.4
KIAA1755	ENST00000496900.2	c.1017G>T	p.Lys339Asn	missense_variant	Exon 3 of 8	2		ENSP00000483264.1

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

GnomAD2 exomes AF: 0.303 AC: 76074 AN: 251022 AF XY: 0.314

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 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

African (AFR) AF: 0.191 AC: 6401 AN: 33454

American (AMR) AF: 0.193 AC: 8643 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 10548 AN: 26128

East Asian (EAS) AF: 0.261 AC: 10351 AN: 39700

South Asian (SAS) AF: 0.372 AC: 32065 AN: 86258

European-Finnish (FIN) AF: 0.320 AC: 17064 AN: 53362

Middle Eastern (MID) AF: 0.514 AC: 2963 AN: 5768

European-Non Finnish (NFE) AF: 0.320 AC: 356175 AN: 1111956

Other (OTH) AF: 0.325 AC: 19605 AN: 60388

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

African (AFR) AF: 0.195 AC: 8115 AN: 41512

American (AMR) AF: 0.245 AC: 3749 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1418 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5166

South Asian (SAS) AF: 0.345 AC: 1665 AN: 4822

European-Finnish (FIN) AF: 0.315 AC: 3339 AN: 10594

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21996 AN: 67974

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.314 Hom.: 27204

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;.
PhyloP100		0.40
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
Mutation Taster		=98/2	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: rs1205434; hg19: chr20-36869516; COSMIC: COSV54076550; COSMIC: COSV54076550;