19-726994-G-C

Variant names:

• chr19-726994-G-C
• rs1342223766
• NM_002579.3:c.58-14G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002579.3(PALM):​c.58-14G>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 0.0037 (0 hom., cov: 29)
  • Exomes 𝑓: 0.10 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALM NM_002579.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.838
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-726994-G-C is Benign according to our data. Variant chr19-726994-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1631069.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM	NM_002579.3	c.58-14G>C		intron_variant	Intron 2 of 8	ENST00000338448.10	NP_002570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10	c.58-14G>C		intron_variant	Intron 2 of 8	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 391 AN: 107426 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00670

Gnomad ASJ AF: 0.00214

Gnomad EAS AF: 0.00477

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00711

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00342

Gnomad OTH AF: 0.00808

GnomAD2 exomes AF: 0.0104 AC: 1189 AN: 113888 AF XY: 0.0103

Gnomad AFR exome AF: 0.00419

Gnomad AMR exome AF: 0.0310

Gnomad ASJ exome AF: 0.00772

Gnomad EAS exome AF: 0.0149

Gnomad FIN exome AF: 0.00611

Gnomad NFE exome AF: 0.00608

Gnomad OTH exome AF: 0.0163

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.101 AC: 33968 AN: 336916 Hom.: 0 Cov.: 8 AF XY: 0.0936 AC XY: 16930 AN XY: 180796

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0758 AC: 667 AN: 8794

American (AMR) AF: 0.0923 AC: 1463 AN: 15854

Ashkenazi Jewish (ASJ) AF: 0.0653 AC: 615 AN: 9416

East Asian (EAS) AF: 0.0864 AC: 829 AN: 9596

South Asian (SAS) AF: 0.0552 AC: 2330 AN: 42226

European-Finnish (FIN) AF: 0.0402 AC: 982 AN: 24432

Middle Eastern (MID) AF: 0.0658 AC: 115 AN: 1748

European-Non Finnish (NFE) AF: 0.121 AC: 25452 AN: 210774

Other (OTH) AF: 0.108 AC: 1515 AN: 14076

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00366 AC: 393 AN: 107486 Hom.: 0 Cov.: 29 AF XY: 0.00399 AC XY: 207 AN XY: 51886

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00226 AC: 64 AN: 28378

American (AMR) AF: 0.00669 AC: 65 AN: 9722

Ashkenazi Jewish (ASJ) AF: 0.00214 AC: 6 AN: 2798

East Asian (EAS) AF: 0.00507 AC: 17 AN: 3350

South Asian (SAS) AF: 0.00382 AC: 12 AN: 3144

European-Finnish (FIN) AF: 0.00711 AC: 41 AN: 5768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.00340 AC: 177 AN: 52114

Other (OTH) AF: 0.00803 AC: 11 AN: 1370

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00780 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.41
PhyloP100		-0.84
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)		0.040		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: rs1342223766; hg19: chr19-726994;