chr6-57046771-T-A

Position:

• chr6-57046771-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020931.4(KIAA1586):​c.16T>A​(p.Ser6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIAA1586 NM_020931.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.396

Genes affected

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

KIAA1586 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04843843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1586	NM_020931.4	c.16T>A	p.Ser6Thr	missense_variant	1/4	ENST00000370733.5	NP_065982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1586	ENST00000370733.5	c.16T>A	p.Ser6Thr	missense_variant	1/4	1	NM_020931.4	ENSP00000359768.4
KIAA1586	ENST00000545356.5	c.16T>A	p.Ser6Thr	missense_variant	1/3	2		ENSP00000445507.1
KIAA1586	ENST00000488682.1	n.25T>A		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2023

The c.16T>A (p.S6T) alteration is located in exon 1 (coding exon 1) of the KIAA1586 gene. This alteration results from a T to A substitution at nucleotide position 16, causing the serine (S) at amino acid position 6 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.0079	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.29	N;N
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D;T
Sift4G	Benign	0.12	T;T
Polyphen		0.0050	B;B
Vest4		0.12
MutPred		0.13		Loss of glycosylation at S6 (P = 0.0711);Loss of glycosylation at S6 (P = 0.0711);
MVP		0.061
MPC		0.23
ClinPred		0.20	T
GERP RS		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.038

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-56911569;