rs566820585

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-727020-C-T
• chr19-727020-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002579.3(PALM):​c.70C>T​(p.Arg24Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,520,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R24Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: PALM NM_002579.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12097031).

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>T	p.Arg24Trp	missense	Exon 3 of 9	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.70C>T	p.Arg24Trp	missense	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>T	p.Arg24Trp	missense	Exon 3 of 9	ENSP00000341911.4	O75781-1
	PALM	ENST00000264560.11	TSL:4	c.70C>T	p.Arg24Trp	missense	Exon 3 of 8	ENSP00000264560.7	O75781-2
	PALM	ENST00000964891.1		c.70C>T	p.Arg24Trp	missense	Exon 3 of 8	ENSP00000634950.1

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150520 Hom.: 0 Cov.: 30

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 3 AN: 146154 AF XY: 0.00

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: 0.0000681

Gnomad NFE exome AF: 0.0000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 15 AN: 1369386 Hom.: 0 Cov.: 32 AF XY: 0.00000887 AC XY: 6 AN XY: 676356

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

American (AMR) AF: 0.00 AC: 0 AN: 35392

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

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35138

South Asian (SAS) AF: 0.00 AC: 0 AN: 78710

European-Finnish (FIN) AF: 0.0000643 AC: 3 AN: 46668

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

European-Non Finnish (NFE) AF: 0.0000104 AC: 11 AN: 1056126

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

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73554

African (AFR) AF: 0.00 AC: 0 AN: 40970

American (AMR) AF: 0.00 AC: 0 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5022

South Asian (SAS) AF: 0.00 AC: 0 AN: 4742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67680

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000185 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.29
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.11
Sift	Benign	0.062	T
Sift4G	Benign	0.12	T
Polyphen		0.36	B
Vest4		0.24
MutPred		0.18		Loss of methylation at K21 (P = 0.0401)
MVP		0.47
MPC		0.18
ClinPred		0.81	D
GERP RS		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.26
Mutation Taster		=89/11	polymorphism

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;