chr6-57052740-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.26 (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
• Publications: 31 publications found

Genes affected

KIAA1586 (HGNC:21360): (KIAA1586) Enables SUMO ligase activity. Involved in protein sumoylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020931.4. 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
	KIAA1586	NM_020931.4	MANE Select	c.241G>A	p.Val81Met	missense	Exon 4 of 4	NP_065982.1
	KIAA1586	NM_001286274.2		c.160G>A	p.Val54Met	missense	Exon 3 of 3	NP_001273203.1
	KIAA1586	NM_001286275.2		c.40G>A	p.Val14Met	missense	Exon 4 of 4	NP_001273204.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1586	ENST00000370733.5	TSL:1 MANE Select	c.241G>A	p.Val81Met	missense	Exon 4 of 4	ENSP00000359768.4
	KIAA1586	ENST00000545356.6	TSL:2	c.160G>A	p.Val54Met	missense	Exon 3 of 3	ENSP00000445507.1
	KIAA1586	ENST00000488682.1	TSL:3	n.395G>A		non_coding_transcript_exon	Exon 4 of 4

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

GnomAD2 exomes AF: 0.221 AC: 52273 AN: 236646 AF XY: 0.218

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 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

African (AFR) AF: 0.348 AC: 11213 AN: 32186

American (AMR) AF: 0.189 AC: 7436 AN: 39348

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5860 AN: 25154

East Asian (EAS) AF: 0.115 AC: 4537 AN: 39494

South Asian (SAS) AF: 0.127 AC: 10332 AN: 81646

European-Finnish (FIN) AF: 0.328 AC: 17381 AN: 52954

Middle Eastern (MID) AF: 0.222 AC: 1261 AN: 5672

European-Non Finnish (NFE) AF: 0.220 AC: 242880 AN: 1102002

Other (OTH) AF: 0.224 AC: 13319 AN: 59430

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

African (AFR) AF: 0.345 AC: 14261 AN: 41384

American (AMR) AF: 0.197 AC: 3017 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 837 AN: 3468

East Asian (EAS) AF: 0.139 AC: 719 AN: 5180

South Asian (SAS) AF: 0.125 AC: 604 AN: 4814

European-Finnish (FIN) AF: 0.350 AC: 3689 AN: 10536

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15290 AN: 67934

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.229 Hom.: 14214

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 v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.32
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.21	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Uncertain	0.024	D
Polyphen		0.0050	B
Vest4		0.089
MPC		0.032
ClinPred		0.013	T
GERP RS		-2.1
Varity_R		0.016
gMVP		0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6926980; hg19: chr6-56917538; COSMIC: COSV66056662;