NM_018216.4:c.207+178G>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018216.4(PANK4):​c.207+178G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 719,502 control chromosomes in the GnomAD database, including 100 homozygotes. 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: 𝑓 0.013 (28 hom., cov: 33)
  • Exomes 𝑓: 0.0099 (72 hom.)
• Consequence: PANK4 NM_018216.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0126 (1925/152318) while in subpopulation SAS AF = 0.0354 (171/4828). AF 95% confidence interval is 0.0311. There are 28 homozygotes in GnomAd4. There are 932 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1925 AD,Unknown gene.

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>C		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>C		intron	N/A	ENSP00000367727.5	Q9NVE7
	PANK4	ENST00000502770.2	TSL:1	n.*70G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000425674.3	D6RJF3
	PANK4	ENST00000502770.2	TSL:1	n.*70G>C		3_prime_UTR	Exon 2 of 3	ENSP00000425674.3	D6RJF3

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1921 AN: 152200 Hom.: 28 Cov.: 33

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.0352

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00989 AC: 5610 AN: 567184 Hom.: 72 Cov.: 6 AF XY: 0.0111 AC XY: 3368 AN XY: 303886

African (AFR) AF: 0.0248 AC: 399 AN: 16118

American (AMR) AF: 0.00206 AC: 70 AN: 33940

Ashkenazi Jewish (ASJ) AF: 0.00193 AC: 32 AN: 16616

East Asian (EAS) AF: 0.0157 AC: 543 AN: 34556

South Asian (SAS) AF: 0.0355 AC: 2091 AN: 58872

European-Finnish (FIN) AF: 0.00513 AC: 184 AN: 35866

Middle Eastern (MID) AF: 0.0192 AC: 69 AN: 3602

European-Non Finnish (NFE) AF: 0.00585 AC: 1972 AN: 337136

Other (OTH) AF: 0.00820 AC: 250 AN: 30478

GnomAD4 genome AF: 0.0126 AC: 1925 AN: 152318 Hom.: 28 Cov.: 33 AF XY: 0.0125 AC XY: 932 AN XY: 74486

African (AFR) AF: 0.0259 AC: 1075 AN: 41572

American (AMR) AF: 0.00379 AC: 58 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5184

South Asian (SAS) AF: 0.0354 AC: 171 AN: 4828

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00606 AC: 412 AN: 68012

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00752 Hom.: 3

Bravo AF: 0.0129

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.52
PhyloP100		0.034
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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;