rs1233749177

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-726995-G-A
• chr19-726995-G-C
• chr19-726995-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002579.3(PALM):​c.58-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 753,664 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 0.0000069 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00000688 AC: 1 AN: 145312 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000493 AC: 3 AN: 608352 Hom.: 0 Cov.: 13 AF XY: 0.00000945 AC XY: 3 AN XY: 317598

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

African (AFR) AF: 0.00 AC: 0 AN: 14644

American (AMR) AF: 0.00 AC: 0 AN: 28854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13848

East Asian (EAS) AF: 0.00 AC: 0 AN: 14680

South Asian (SAS) AF: 0.00 AC: 0 AN: 65270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2524

European-Non Finnish (NFE) AF: 0.00000726 AC: 3 AN: 413404

Other (OTH) AF: 0.00 AC: 0 AN: 25030

⚠️ 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 AF: 0.00000688 AC: 1 AN: 145312 Hom.: 0 Cov.: 31 AF XY: 0.0000141 AC XY: 1 AN XY: 70806

African (AFR) AF: 0.00 AC: 0 AN: 40242

American (AMR) AF: 0.00 AC: 0 AN: 14686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 4338

South Asian (SAS) AF: 0.00 AC: 0 AN: 4060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66106

Other (OTH) AF: 0.00 AC: 0 AN: 2032

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.38
PhyloP100		-0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1233749177; hg19: chr19-726995;