1-2521540-C-T

Variant names:

• chr1-2521540-C-T
• rs12073504
• NM_018216.4:c.207+178G>A

Variant summary

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

The NM_018216.4(PANK4):​c.207+178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 567,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: PANK4 NM_018216.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 0 publications found

Genes affected

PANK4 (HGNC:19366): (pantothenate kinase 4 (inactive)) This gene encodes a protein belonging to the pantothenate kinase family. Pantothenate kinase is a key regulatory enzyme in the biosynthesis of coenzyme A (CoA) in bacteria and mammalian cells. It catalyzes the first committed step in the universal biosynthetic pathway leading to CoA and is itself subject to regulation through feedback inhibition by CoA. This family member is most abundant in muscle but is expressed in all tissues. [provided by RefSeq, Jul 2008]

PANK4 Gene-Disease associations (from GenCC):

• early-onset posterior polar cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cataract

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• cataract 49

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018216.4. 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
	PANK4	NM_018216.4	MANE Select	c.207+178G>A		intron	N/A	NP_060686.3	Q9NVE7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PANK4	ENST00000378466.9	TSL:1 MANE Select	c.207+178G>A		intron	N/A	ENSP00000367727.5	Q9NVE7
	PANK4	ENST00000502770.2	TSL:1	n.*70G>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000425674.3	D6RJF3
	PANK4	ENST00000502770.2	TSL:1	n.*70G>A		3_prime_UTR	Exon 2 of 3	ENSP00000425674.3	D6RJF3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000176 AC: 1 AN: 567196 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 303894

African (AFR) AF: 0.00 AC: 0 AN: 16118

American (AMR) AF: 0.0000295 AC: 1 AN: 33940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16616

East Asian (EAS) AF: 0.00 AC: 0 AN: 34558

South Asian (SAS) AF: 0.00 AC: 0 AN: 58876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35866

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3602

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 337140

Other (OTH) AF: 0.00 AC: 0 AN: 30480

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.7
DANN	Benign	0.62
PhyloP100		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs12073504; hg19: chr1-2452979;