7-95586935-A-T

Variant names:

• chr7-95586935-A-T
• rs10247649
• NM_002612.4:c.1095+75T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002612.4(PDK4):​c.1095+75T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDK4 NM_002612.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 9 publications found

Genes affected

PDK4 (HGNC:8812): (pyruvate dehydrogenase kinase 4) This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq, Jul 2008]

PDK4-AS1 (HGNC:55767): (PDK4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002612.4. 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
	PDK4	NM_002612.4	MANE Select	c.1095+75T>A		intron	N/A	NP_002603.1	A4D1H4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDK4	ENST00000005178.6	TSL:1 MANE Select	c.1095+75T>A		intron	N/A	ENSP00000005178.5	Q16654
	PDK4	ENST00000886049.1		c.1095+75T>A		intron	N/A	ENSP00000556108.1
	PDK4	ENST00000886050.1		c.1089+75T>A		intron	N/A	ENSP00000556109.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 652622 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 347230

African (AFR) AF: 0.00 AC: 0 AN: 17190

American (AMR) AF: 0.00 AC: 0 AN: 33936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17788

East Asian (EAS) AF: 0.00 AC: 0 AN: 35330

South Asian (SAS) AF: 0.00 AC: 0 AN: 59816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3774

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 401892

Other (OTH) AF: 0.00 AC: 0 AN: 33082

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.44
PhyloP100		0.091

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10247649;

hg19: chr7-95216247;