19-726999-T-C

Variant names:

• chr19-726999-T-C
• rs1210670058
• NM_002579.3:c.58-9T>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.58-9T>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 0.0031 (0 hom., cov: 25)
  • Exomes 𝑓: 0.051 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALM NM_002579.3 intron
• Scores: Splicing: ADA: 0.00002592
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.267
• 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=-0.96).
• BP6: Variant 19-726999-T-C is Benign according to our data. Variant chr19-726999-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2807193.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.58-9T>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.58-9T>C		intron_variant	Intron 2 of 8	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 253 AN: 82148 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.00183

Gnomad AMR AF: 0.00631

Gnomad ASJ AF: 0.00185

Gnomad EAS AF: 0.00304

Gnomad SAS AF: 0.00241

Gnomad FIN AF: 0.00864

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00214

Gnomad OTH AF: 0.00768

GnomAD2 exomes AF: 0.00511 AC: 566 AN: 110684 AF XY: 0.00507

Gnomad AFR exome AF: 0.00222

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.00227

Gnomad EAS exome AF: 0.00726

Gnomad FIN exome AF: 0.00274

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00922

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0510 AC: 17158 AN: 336446 Hom.: 0 Cov.: 11 AF XY: 0.0499 AC XY: 8958 AN XY: 179424

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

African (AFR) AF: 0.0322 AC: 289 AN: 8964

American (AMR) AF: 0.0491 AC: 781 AN: 15910

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 382 AN: 9382

East Asian (EAS) AF: 0.0405 AC: 389 AN: 9596

South Asian (SAS) AF: 0.0588 AC: 2372 AN: 40364

European-Finnish (FIN) AF: 0.0366 AC: 899 AN: 24558

Middle Eastern (MID) AF: 0.0438 AC: 82 AN: 1874

European-Non Finnish (NFE) AF: 0.0526 AC: 11129 AN: 211698

Other (OTH) AF: 0.0592 AC: 835 AN: 14100

⚠️ 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: 0.00308 AC: 253 AN: 82202 Hom.: 0 Cov.: 25 AF XY: 0.00311 AC XY: 123 AN XY: 39534

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

African (AFR) AF: 0.00295 AC: 63 AN: 21388

American (AMR) AF: 0.00630 AC: 43 AN: 6830

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 4 AN: 2166

East Asian (EAS) AF: 0.00304 AC: 9 AN: 2962

South Asian (SAS) AF: 0.00281 AC: 7 AN: 2490

European-Finnish (FIN) AF: 0.00864 AC: 31 AN: 3590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.00212 AC: 87 AN: 41056

Other (OTH) AF: 0.00762 AC: 8 AN: 1050

⚠️ 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: 0.0379 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 25, 2023

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	-0.96
CADD	Benign	5.7
DANN	Benign	0.47
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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: rs1210670058; hg19: chr19-726999;