chr1-26122331-G-C

Position:

• chr1-26122331-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_152835.5(PDIK1L):​c.780G>C​(p.Glu260Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PDIK1L NM_152835.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, PDIK1L
• BP4: Computational evidence support a benign effect (MetaRNN=0.15341151).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDIK1L	NM_152835.5	c.780G>C	p.Glu260Asp	missense_variant	3/3	ENST00000374269.2
PDIK1L	NM_001243532.2	c.780G>C	p.Glu260Asp	missense_variant	3/3
PDIK1L	NM_001243533.2	c.780G>C	p.Glu260Asp	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDIK1L	ENST00000374269.2	c.780G>C	p.Glu260Asp	missense_variant	3/3	1	NM_152835.5	P1
PDIK1L	ENST00000374271.8	c.780G>C	p.Glu260Asp	missense_variant	4/4	1		P1
PDIK1L	ENST00000619836.4	c.780G>C	p.Glu260Asp	missense_variant	3/3	3		P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 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: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000192

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;.;.
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N;N
MutationTaster	Benign	0.78	N;N
PrimateAI	Pathogenic	0.82	D
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.32
MutPred		0.36		Loss of methylation at K263 (P = 0.0871);Loss of methylation at K263 (P = 0.0871);Loss of methylation at K263 (P = 0.0871);
MVP		0.73
MPC		1.0
ClinPred		0.58	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.75

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: rs2088002346; hg19: chr1-26448822;