chr19-726990-A-C

Position:

• chr19-726990-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002579.3(PALM):​c.58-18A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 30)
  • Exomes 𝑓: 0.11 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALM NM_002579.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.67

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-726990-A-C is Benign according to our data. Variant chr19-726990-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1628350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM	NM_002579.3	c.58-18A>C		intron_variant		ENST00000338448.10	NP_002570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10	c.58-18A>C		intron_variant		1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 539 AN: 118812 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00341

Gnomad AMI AF: 0.00704

Gnomad AMR AF: 0.00520

Gnomad ASJ AF: 0.00235

Gnomad EAS AF: 0.0132

Gnomad SAS AF: 0.0100

Gnomad FIN AF: 0.00764

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00512

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.105 AC: 41061 AN: 391052 Hom.: 0 Cov.: 8 AF XY: 0.0951 AC XY: 20027 AN XY: 210506

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.0739

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.0667

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00454 AC: 540 AN: 118880 Hom.: 0 Cov.: 30 AF XY: 0.00461 AC XY: 264 AN XY: 57240

Gnomad4 AFR AF: 0.00340

Gnomad4 AMR AF: 0.00519

Gnomad4 ASJ AF: 0.00235

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.0103

Gnomad4 FIN AF: 0.00764

Gnomad4 NFE AF: 0.00382

Gnomad4 OTH AF: 0.00507

Alfa AF: 0.0134 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 07, 2025	- -
Likely 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	-0.91
CADD	Benign	0.088
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1169108954; hg19: chr19-726990;