2-219602471-C-T

Variant names:

• chr2-219602471-C-T
• NM_052902.4:c.442C>T

Variant summary

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

The NM_052902.4(STK11IP):​c.442C>T​(p.Leu148Phe) 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 1,460,820 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STK11IP NM_052902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

Genes affected

STK11IP (HGNC:19184): (serine/threonine kinase 11 interacting protein) Enables protein kinase binding activity. Involved in protein localization. Located in cytoplasm and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

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
STK11IP	NM_052902.4	c.442C>T	p.Leu148Phe	missense_variant	Exon 6 of 25	ENST00000456909.6	NP_443134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STK11IP	ENST00000456909.6	c.442C>T	p.Leu148Phe	missense_variant	Exon 6 of 25	1	NM_052902.4	ENSP00000389383.1
STK11IP	ENST00000459692.1	n.448C>T		non_coding_transcript_exon_variant	Exon 5 of 8	5
STK11IP	ENST00000468584.5	n.465C>T		non_coding_transcript_exon_variant	Exon 5 of 6	3
STK11IP	ENST00000475396.5	n.423C>T		non_coding_transcript_exon_variant	Exon 5 of 16	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460820 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.475C>T (p.L159F) alteration is located in exon 6 (coding exon 6) of the STK11IP gene. This alteration results from a C to T substitution at nucleotide position 475, causing the leucine (L) at amino acid position 159 to be replaced by a phenylalanine (F). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.2	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0020	D
Vest4		0.56
MVP		0.061
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.16
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-220467193;