NM_020931.4:c.116C>G

Variant names:

• chr6-57050784-C-G
• rs150587796
• NM_020931.4:c.116C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020931.4(KIAA1586):​c.116C>G​(p.Ser39Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S39L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIAA1586 NM_020931.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18295929).

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.116C>G	p.Ser39Trp	missense	Exon 3 of 4	NP_065982.1	Q9HCI6-1
	KIAA1586	NM_001286275.2		c.-86C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001273204.1
	KIAA1586	NM_001286276.2		c.-86C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001273205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA1586	ENST00000370733.5	TSL:1 MANE Select	c.116C>G	p.Ser39Trp	missense	Exon 3 of 4	ENSP00000359768.4	Q9HCI6-1
	KIAA1586	ENST00000928058.1		c.209C>G	p.Ser70Trp	missense	Exon 4 of 5	ENSP00000598117.1
	KIAA1586	ENST00000928059.1		c.128C>G	p.Ser43Trp	missense	Exon 3 of 4	ENSP00000598118.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459796 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726378

African (AFR) AF: 0.00 AC: 0 AN: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110360

Other (OTH) AF: 0.00 AC: 0 AN: 60300

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.034	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-2.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.068
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.41
MutPred		0.33		Loss of disorder (P = 4e-04)
MVP		0.16
MPC		0.27
ClinPred		0.62	D
GERP RS		-0.78
Varity_R		0.074
gMVP		0.030
Mutation Taster		=95/5	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: rs150587796; hg19: chr6-56915582;