6-57050775-A-G

Position:

• chr6-57050775-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020931.4(KIAA1586):​c.107A>G​(p.Glu36Gly) variant causes a missense, splice region 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. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KIAA1586 NM_020931.4 missense, splice_region
• Scores: Splicing: ADA: 0.0003016
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2145882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIAA1586	NM_020931.4	c.107A>G	p.Glu36Gly	missense_variant, splice_region_variant	3/4	ENST00000370733.5	NP_065982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIAA1586	ENST00000370733.5	c.107A>G	p.Glu36Gly	missense_variant, splice_region_variant	3/4	1	NM_020931.4	ENSP00000359768.4
KIAA1586	ENST00000545356.5	c.106-1911A>G		intron_variant		2		ENSP00000445507.1
KIAA1586	ENST00000488682.1	n.261A>G		splice_region_variant, non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

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

Sep 27, 2021

The c.107A>G (p.E36G) alteration is located in exon 3 (coding exon 3) of the KIAA1586 gene. This alteration results from a A to G substitution at nucleotide position 107, causing the glutamic acid (E) at amino acid position 36 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.061
Sift	Benign	0.35	T
Sift4G	Benign	0.31	T
Polyphen		0.061	B
Vest4		0.57
MutPred		0.21		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.32
MPC		0.26
ClinPred		0.64	D
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.037
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00030
dbscSNV1_RF	Benign	0.054
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: chr6-56915573;