11-116849247-G-T

Variant names:

• chr11-116849247-G-T
• rs766444475
• NM_001366686.3:c.3692C>A

Variant summary

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

The NM_001366686.3(SIK3):​c.3692C>A​(p.Pro1231Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. P1231L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIK3 NM_001366686.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 1 publications found

Genes affected

SIK3 (HGNC:29165): (SIK family kinase 3) Enables ATP binding activity; magnesium ion binding activity; and protein serine/threonine kinase activity. Involved in positive regulation of TORC1 signaling; positive regulation of TORC2 signaling; and protein phosphorylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

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=0.20801127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIK3	NM_001366686.3	c.3692C>A	p.Pro1231Gln	missense_variant	Exon 22 of 25	ENST00000445177.6	NP_001353615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SIK3	ENST00000445177.6	c.3692C>A	p.Pro1231Gln	missense_variant	Exon 22 of 25	5	NM_001366686.3	ENSP00000391295.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.98
Eigen	Benign	-0.072
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.67	T
PhyloP100		4.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0040	D;D
Vest4		0.53
MVP		0.20
ClinPred		0.61	D
GERP RS		4.9
PromoterAI		0.0028	Neutral
Varity_R		0.20
gMVP		0.23
Mutation Taster		=78/22	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: rs766444475; hg19: chr11-116719963;