6-57052710-C-T

Variant names:

• chr6-57052710-C-T
• rs61741654
• NM_020931.4:c.211C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6 BS2

The NM_020931.4(KIAA1586):​c.211C>T​(p.Arg71*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 1,566,780 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0028 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (5 hom.)
• Consequence: KIAA1586 NM_020931.4 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.16
• Publications: 5 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: Likely_benign. The variant received -5 ACMG points.

• BP6: Variant 6-57052710-C-T is Benign according to our data. Variant chr6-57052710-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3045280.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1586	NM_020931.4	MANE Select	c.211C>T	p.Arg71*	stop_gained	Exon 4 of 4	NP_065982.1	Q9HCI6-1
	KIAA1586	NM_001286274.2		c.130C>T	p.Arg44*	stop_gained	Exon 3 of 3	NP_001273203.1	F5H2N6
	KIAA1586	NM_001286275.2		c.10C>T	p.Arg4*	stop_gained	Exon 4 of 4	NP_001273204.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1586	ENST00000370733.5	TSL:1 MANE Select	c.211C>T	p.Arg71*	stop_gained	Exon 4 of 4	ENSP00000359768.4	Q9HCI6-1
	KIAA1586	ENST00000928058.1		c.304C>T	p.Arg102*	stop_gained	Exon 5 of 5	ENSP00000598117.1
	KIAA1586	ENST00000928059.1		c.223C>T	p.Arg75*	stop_gained	Exon 4 of 4	ENSP00000598118.1

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 428 AN: 152010 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00977

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000749 AC: 168 AN: 224268 AF XY: 0.000631

Gnomad AFR exome AF: 0.00971

Gnomad AMR exome AF: 0.000190

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000592

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000660

Gnomad OTH exome AF: 0.000380

GnomAD4 exome AF: 0.000278 AC: 393 AN: 1414652 Hom.: 5 Cov.: 30 AF XY: 0.000245 AC XY: 172 AN XY: 700740

African (AFR) AF: 0.00975 AC: 305 AN: 31292

American (AMR) AF: 0.000228 AC: 8 AN: 35118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24156

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39202

South Asian (SAS) AF: 0.000102 AC: 8 AN: 78074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52406

Middle Eastern (MID) AF: 0.000363 AC: 2 AN: 5514

European-Non Finnish (NFE) AF: 0.0000358 AC: 39 AN: 1090592

Other (OTH) AF: 0.000515 AC: 30 AN: 58298

GnomAD4 genome AF: 0.00283 AC: 430 AN: 152128 Hom.: 3 Cov.: 32 AF XY: 0.00274 AC XY: 204 AN XY: 74362

African (AFR) AF: 0.00979 AC: 406 AN: 41492

American (AMR) AF: 0.000654 AC: 10 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67976

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.00306

ESP6500AA AF: 0.00977 AC: 43

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000857 AC: 104

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	KIAA1586-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	29
DANN	Uncertain	1.0
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.013	N
PhyloP100		-1.2
Vest4		0.056
GERP RS		-2.2
Mutation Taster		=186/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61741654; hg19: chr6-56917508; COSMIC: COSV100875282;