rs6926980

Variant names:

• chr6-57052740-G-A
• rs6926980
• NM_020931.4:c.241G>A

Variant summary

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

The NM_020931.4(KIAA1586):​c.241G>A​(p.Val81Met) 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 1,589,804 control chromosomes in the GnomAD database, including 41,445 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5438 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36007 hom.)
• Consequence: KIAA1586 NM_020931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

Genes affected

KIAA1586 (HGNC:21360): (KIAA1586) Enables SUMO ligase activity. Involved in protein sumoylation. [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=0.003326118).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIAA1586	NM_020931.4	c.241G>A	p.Val81Met	missense_variant	Exon 4 of 4	ENST00000370733.5	NP_065982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIAA1586	ENST00000370733.5	c.241G>A	p.Val81Met	missense_variant	Exon 4 of 4	1	NM_020931.4	ENSP00000359768.4
KIAA1586	ENST00000545356.5	c.160G>A	p.Val54Met	missense_variant	Exon 3 of 3	2		ENSP00000445507.1
KIAA1586	ENST00000488682.1	n.395G>A		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39167 AN: 151800 Hom.: 5424 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.242

GnomAD3 exomes AF: 0.221 AC: 52273 AN: 236646 Hom.: 6392 AF XY: 0.218 AC XY: 27901 AN XY: 128268

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.184

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.131

Gnomad SAS exome AF: 0.127

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.219 AC: 314219 AN: 1437886 Hom.: 36007 Cov.: 33 AF XY: 0.215 AC XY: 153856 AN XY: 713960

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.328

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.224

GnomAD4 genome AF: 0.258 AC: 39224 AN: 151918 Hom.: 5438 Cov.: 32 AF XY: 0.258 AC XY: 19148 AN XY: 74238

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.241

Alfa AF: 0.223 Hom.: 7261

Bravo AF: 0.254

TwinsUK AF: 0.226 AC: 837

ALSPAC AF: 0.206 AC: 792

ESP6500AA AF: 0.338 AC: 1488

ESP6500EA AF: 0.228 AC: 1960

ExAC AF: 0.223 AC: 27033

Asia WGS AF: 0.155 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.9
DANN	Benign	0.31
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.50	T;T
MetaRNN	Benign	0.0033	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	.;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.024
Sift	Benign	1.0	T;T
Sift4G	Uncertain	0.024	D;D
Polyphen		0.0050	B;B
Vest4		0.089
MPC		0.032
ClinPred		0.013	T
GERP RS		-2.1
Varity_R		0.016
gMVP		0.029

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6926980; hg19: chr6-56917538; COSMIC: COSV66056662;