19-726200-G-A

Position:

• chr19-726200-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002579.3(PALM):​c.57+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,611,798 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (467 hom., cov: 32)
  • Exomes 𝑓: 0.016 (561 hom.)
• Consequence: PALM NM_002579.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.210

Genes affected

PALM (HGNC:8594): (paralemmin) This gene encodes a member of the paralemmin protein family. The product of this gene is a prenylated and palmitoylated phosphoprotein that associates with the cytoplasmic face of plasma membranes and is implicated in plasma membrane dynamics in neurons and other cell types. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Jul 2008]

PALM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-726200-G-A is Benign according to our data. Variant chr19-726200-G-A is described in ClinVar as [Benign]. Clinvar id is 1168478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM	NM_002579.3	c.57+11G>A		intron_variant		ENST00000338448.10	NP_002570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10	c.57+11G>A		intron_variant		1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7751 AN: 152138 Hom.: 465 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0197 AC: 4903 AN: 248918 Hom.: 206 AF XY: 0.0172 AC XY: 2322 AN XY: 135138

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.0158

Gnomad ASJ exome AF: 0.00982

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.00659

Gnomad NFE exome AF: 0.0140

Gnomad OTH exome AF: 0.0171

GnomAD4 exome AF: 0.0155 AC: 22649 AN: 1459542 Hom.: 561 Cov.: 30 AF XY: 0.0149 AC XY: 10844 AN XY: 726182

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.00938

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00147

Gnomad4 FIN exome AF: 0.00674

Gnomad4 NFE exome AF: 0.0131

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0510 AC: 7771 AN: 152256 Hom.: 467 Cov.: 32 AF XY: 0.0491 AC XY: 3655 AN XY: 74442

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.00894

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0393 Hom.: 104

Bravo AF: 0.0589

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.8
DANN	Benign	0.58

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: rs10408458; hg19: chr19-726200;