chr19-727020-C-A

Variant names:

• chr19-727020-C-A
• rs566820585
• NM_002579.3:c.70C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002579.3(PALM):​c.70C>A​(p.Arg24Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,369,384 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PALM NM_002579.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.291 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002579.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM	NM_002579.3	MANE Select	c.70C>A	p.Arg24Arg	synonymous	Exon 3 of 9	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.70C>A	p.Arg24Arg	synonymous	Exon 3 of 8	NP_001035224.1	O75781-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM	ENST00000338448.10	TSL:1 MANE Select	c.70C>A	p.Arg24Arg	synonymous	Exon 3 of 9	ENSP00000341911.4	O75781-1
	PALM	ENST00000264560.11	TSL:4	c.70C>A	p.Arg24Arg	synonymous	Exon 3 of 8	ENSP00000264560.7	O75781-2
	PALM	ENST00000964891.1		c.70C>A	p.Arg24Arg	synonymous	Exon 3 of 8	ENSP00000634950.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1369384 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 676356

African (AFR) AF: 0.00 AC: 0 AN: 30938

American (AMR) AF: 0.00 AC: 0 AN: 35394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24702

East Asian (EAS) AF: 0.00 AC: 0 AN: 35138

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5138

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1056122

Other (OTH) AF: 0.00 AC: 0 AN: 56574

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.5
DANN	Benign	0.58
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs566820585; hg19: chr19-727020;