2-219598138-G-T

Variant names:

• chr2-219598138-G-T
• rs1697855777
• NM_052902.4:c.19G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052902.4(STK11IP):​c.19G>T​(p.Asp7Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000189 in 1,589,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D7V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: STK11IP NM_052902.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052902.4. 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
	STK11IP	NM_052902.4	MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 2 of 25	NP_443134.3	Q8N1F8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STK11IP	ENST00000456909.6	TSL:1 MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 2 of 25	ENSP00000389383.1	Q8N1F8
	STK11IP	ENST00000879651.1		c.19G>T	p.Asp7Tyr	missense	Exon 2 of 25	ENSP00000549710.1
	STK11IP	ENST00000879655.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 24	ENSP00000549714.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437758 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713316

African (AFR) AF: 0.00 AC: 0 AN: 32590

American (AMR) AF: 0.00 AC: 0 AN: 41538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25566

East Asian (EAS) AF: 0.00 AC: 0 AN: 37850

South Asian (SAS) AF: 0.00 AC: 0 AN: 82510

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 51986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100622

Other (OTH) AF: 0.00 AC: 0 AN: 59360

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-1.1	T
PhyloP100		4.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Vest4		0.80
MVP		0.14
ClinPred		0.96	D
GERP RS		3.6
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.59
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1697855777; hg19: chr2-220462860;