chr19-726990-A-C

Variant names:

• chr19-726990-A-C
• rs1169108954
• NM_002579.3:c.58-18A>C

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PALM	NM_002579.3	c.58-18A>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.58-18A>C		intron_variant	Intron 2 of 8	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 539 AN: 118812 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.0109 AC: 1413 AN: 129286 AF XY: 0.0102

Gnomad AFR exome AF: 0.00503

Gnomad AMR exome AF: 0.0318

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.0111

Gnomad FIN exome AF: 0.00657

Gnomad NFE exome AF: 0.00678

Gnomad OTH exome AF: 0.0173

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

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

African (AFR) AF: 0.0953 AC: 945 AN: 9914

American (AMR) AF: 0.0687 AC: 1459 AN: 21250

Ashkenazi Jewish (ASJ) AF: 0.0739 AC: 834 AN: 11292

East Asian (EAS) AF: 0.115 AC: 1595 AN: 13892

South Asian (SAS) AF: 0.0231 AC: 1232 AN: 53428

European-Finnish (FIN) AF: 0.0667 AC: 1925 AN: 28850

Middle Eastern (MID) AF: 0.0817 AC: 150 AN: 1836

European-Non Finnish (NFE) AF: 0.132 AC: 30922 AN: 233422

Other (OTH) AF: 0.116 AC: 1999 AN: 17168

⚠️ 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: 0.00454 AC: 540 AN: 118880 Hom.: 0 Cov.: 30 AF XY: 0.00461 AC XY: 264 AN XY: 57240

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

African (AFR) AF: 0.00340 AC: 109 AN: 32044

American (AMR) AF: 0.00519 AC: 58 AN: 11172

Ashkenazi Jewish (ASJ) AF: 0.00235 AC: 7 AN: 2974

East Asian (EAS) AF: 0.0137 AC: 50 AN: 3646

South Asian (SAS) AF: 0.0103 AC: 36 AN: 3492

European-Finnish (FIN) AF: 0.00764 AC: 49 AN: 6412

Middle Eastern (MID) AF: 0.00800 AC: 2 AN: 250

European-Non Finnish (NFE) AF: 0.00382 AC: 216 AN: 56602

Other (OTH) AF: 0.00507 AC: 8 AN: 1578

⚠️ 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: 0.0134 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.088
DANN	Benign	0.30
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1169108954; hg19: chr19-726990;