rs1342223766

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-726994-G-A
• chr19-726994-G-C
• chr19-726994-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002579.3(PALM):​c.58-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 485,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000046 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: PALM NM_002579.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 5 AN: 108398 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000878 AC: 1 AN: 113888 AF XY: 0.0000162

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 AF: 0.0000265 AC: 10 AN: 376772 Hom.: 0 Cov.: 8 AF XY: 0.0000249 AC XY: 5 AN XY: 200882

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

African (AFR) AF: 0.000104 AC: 1 AN: 9594

American (AMR) AF: 0.00 AC: 0 AN: 16966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10024

East Asian (EAS) AF: 0.00 AC: 0 AN: 10468

South Asian (SAS) AF: 0.0000452 AC: 2 AN: 44230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1848

European-Non Finnish (NFE) AF: 0.0000288 AC: 7 AN: 242712

Other (OTH) AF: 0.00 AC: 0 AN: 15694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000010), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000461 AC: 5 AN: 108398 Hom.: 0 Cov.: 29 AF XY: 0.0000382 AC XY: 2 AN XY: 52324

African (AFR) AF: 0.000105 AC: 3 AN: 28594

American (AMR) AF: 0.00 AC: 0 AN: 9876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2814

East Asian (EAS) AF: 0.00 AC: 0 AN: 3374

South Asian (SAS) AF: 0.00 AC: 0 AN: 3154

European-Finnish (FIN) AF: 0.000171 AC: 1 AN: 5854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.0000191 AC: 1 AN: 52482

Other (OTH) AF: 0.00 AC: 0 AN: 1382

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Uncertain	24
DANN	Benign	0.48
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.78		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.78		Position offset: 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;