chr1-114776441-C-T

Variant names:

• chr1-114776441-C-T
• rs141025380
• NM_025073.3:c.427G>A

Variant summary

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

The NM_025073.3(SIKE1):​c.427G>A​(p.Asp143Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D143H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SIKE1 NM_025073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

Genes affected

SIKE1 (HGNC:26119): (suppressor of IKBKE 1) SIKE interacts with IKK-epsilon (IKBKE; MIM 605048) and TBK1 (MIM 604834) and acts as a suppressor of TLR3 (MIM 603029) and virus-triggered interferon activation pathways (Huang et al., 2005 [PubMed 16281057]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIKE1	NM_025073.3	c.427G>A	p.Asp143Asn	missense_variant	Exon 4 of 5	ENST00000060969.6	NP_079349.2
SIKE1	NM_001102396.2	c.439G>A	p.Asp147Asn	missense_variant	Exon 4 of 5		NP_001095866.1
SIKE1	NR_049741.2	n.567G>A		non_coding_transcript_exon_variant	Exon 4 of 5
SIKE1	NR_049742.2	n.399G>A		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIKE1	ENST00000060969.6	c.427G>A	p.Asp143Asn	missense_variant	Exon 4 of 5	1	NM_025073.3	ENSP00000060969.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251250 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135830

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458496 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.58	D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.3	.;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.0	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.028	D;D
Polyphen		0.99	D;D
Vest4		0.39
MutPred		0.59		.;Loss of disorder (P = 0.0857);
MVP		0.86
MPC		1.1
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.43
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs141025380; hg19: chr1-115319062;