6-57053109-C-T

Variant names:

• chr6-57053109-C-T
• rs61748913
• NM_020931.4:c.610C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_020931.4(KIAA1586):​c.610C>T​(p.Arg204*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,605,896 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0063 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00068 (11 hom.)
• Consequence: KIAA1586 NM_020931.4 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.47
• Publications: 2 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 -9 ACMG points.

• BP6: Variant 6-57053109-C-T is Benign according to our data. Variant chr6-57053109-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3037814.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00627 (949/151282) while in subpopulation AFR AF = 0.0217 (896/41228). AF 95% confidence interval is 0.0206. There are 10 homozygotes in GnomAd4. There are 445 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 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.610C>T	p.Arg204*	stop_gained	Exon 4 of 4	NP_065982.1	Q9HCI6-1
	KIAA1586	NM_001286274.2		c.529C>T	p.Arg177*	stop_gained	Exon 3 of 3	NP_001273203.1	F5H2N6
	KIAA1586	NM_001286275.2		c.409C>T	p.Arg137*	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.610C>T	p.Arg204*	stop_gained	Exon 4 of 4	ENSP00000359768.4	Q9HCI6-1
	KIAA1586	ENST00000928058.1		c.703C>T	p.Arg235*	stop_gained	Exon 5 of 5	ENSP00000598117.1
	KIAA1586	ENST00000928059.1		c.622C>T	p.Arg208*	stop_gained	Exon 4 of 4	ENSP00000598118.1

Frequencies

GnomAD3 genomes AF: 0.00626 AC: 947 AN: 151164 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00531

GnomAD2 exomes AF: 0.00171 AC: 418 AN: 244588 AF XY: 0.00119

Gnomad AFR exome AF: 0.0230

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.0000807

Gnomad OTH exome AF: 0.000339

GnomAD4 exome AF: 0.000685 AC: 996 AN: 1454614 Hom.: 11 Cov.: 33 AF XY: 0.000593 AC XY: 429 AN XY: 723670

African (AFR) AF: 0.0236 AC: 772 AN: 32746

American (AMR) AF: 0.00137 AC: 58 AN: 42440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.0000824 AC: 7 AN: 84992

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53264

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5720

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1110036

Other (OTH) AF: 0.00168 AC: 101 AN: 59992

GnomAD4 genome AF: 0.00627 AC: 949 AN: 151282 Hom.: 10 Cov.: 32 AF XY: 0.00602 AC XY: 445 AN XY: 73860

African (AFR) AF: 0.0217 AC: 896 AN: 41228

American (AMR) AF: 0.00183 AC: 28 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000207 AC: 14 AN: 67744

Other (OTH) AF: 0.00525 AC: 11 AN: 2094

Alfa AF: 0.00268 Hom.: 6

Bravo AF: 0.00725

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00194 AC: 236

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

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	Benign	-0.24	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.96
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.0046	N
PhyloP100		-3.5
Vest4		0.048
GERP RS		-3.1
Mutation Taster		=189/11	polymorphism

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: rs61748913; hg19: chr6-56917907;