chr19-726995-G-C

Variant names:

• chr19-726995-G-C
• rs1233749177
• NM_002579.3:c.58-13G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002579.3(PALM):​c.58-13G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALM NM_002579.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM	NM_002579.3	c.58-13G>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.58-13G>C		intron_variant	Intron 2 of 8	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes AF: 0.000262 AC: 38 AN: 145170 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000273

Gnomad ASJ AF: 0.000295

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000216

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.000492

GnomAD2 exomes AF: 0.0000135 AC: 2 AN: 148370 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000816

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00892 AC: 5267 AN: 590420 Hom.: 0 Cov.: 13 AF XY: 0.00815 AC XY: 2518 AN XY: 308964

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

African (AFR) AF: 0.00762 AC: 109 AN: 14296

American (AMR) AF: 0.00129 AC: 37 AN: 28732

Ashkenazi Jewish (ASJ) AF: 0.00571 AC: 78 AN: 13672

East Asian (EAS) AF: 0.00711 AC: 102 AN: 14338

South Asian (SAS) AF: 0.00159 AC: 103 AN: 64882

European-Finnish (FIN) AF: 0.00302 AC: 90 AN: 29790

Middle Eastern (MID) AF: 0.00447 AC: 11 AN: 2460

European-Non Finnish (NFE) AF: 0.0113 AC: 4505 AN: 397924

Other (OTH) AF: 0.00954 AC: 232 AN: 24326

⚠️ 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: 0.000268 AC: 39 AN: 145318 Hom.: 0 Cov.: 31 AF XY: 0.000310 AC XY: 22 AN XY: 70878

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

African (AFR) AF: 0.000124 AC: 5 AN: 40336

American (AMR) AF: 0.000272 AC: 4 AN: 14698

Ashkenazi Jewish (ASJ) AF: 0.000295 AC: 1 AN: 3386

East Asian (EAS) AF: 0.00139 AC: 6 AN: 4316

South Asian (SAS) AF: 0.00123 AC: 5 AN: 4060

European-Finnish (FIN) AF: 0.000216 AC: 2 AN: 9270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000227 AC: 15 AN: 66040

Other (OTH) AF: 0.000487 AC: 1 AN: 2054

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.28
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1233749177; hg19: chr19-726995;