chr1-26114504-A-T

Position:

• chr1-26114504-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP2 PP3_Strong

The NM_152835.5(PDIK1L):​c.196A>T​(p.Asn66Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDIK1L NM_152835.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

Genes affected

PDIK1L (HGNC:18981): (PDLIM1 interacting kinase 1 like) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in meiotic cell cycle. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PDIK1L
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIK1L	NM_152835.5	c.196A>T	p.Asn66Tyr	missense_variant	2/3	ENST00000374269.2
PDIK1L	NM_001243532.2	c.196A>T	p.Asn66Tyr	missense_variant	2/3
PDIK1L	NM_001243533.2	c.196A>T	p.Asn66Tyr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIK1L	ENST00000374269.2	c.196A>T	p.Asn66Tyr	missense_variant	2/3	1	NM_152835.5	P1
PDIK1L	ENST00000374271.8	c.196A>T	p.Asn66Tyr	missense_variant	3/4	1		P1
PDIK1L	ENST00000619836.4	c.196A>T	p.Asn66Tyr	missense_variant	2/3	3		P1
PDIK1L	ENST00000444713.5	c.196A>T	p.Asn66Tyr	missense_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2022

The c.196A>T (p.N66Y) alteration is located in exon 2 (coding exon 1) of the PDIK1L gene. This alteration results from a A to T substitution at nucleotide position 196, causing the asparagine (N) at amino acid position 66 to be replaced by a tyrosine (Y). 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	0.45
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;T;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D;.;.
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	2.0	M;.;M;M
MutationTaster	Benign	0.85	D;D
PrimateAI	Pathogenic	0.82	D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.99	D;.;D;D
Vest4		0.90
MutPred		0.92		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.77
MPC		2.5
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-26440995;