NM_002579.3:c.71G>A

Variant names:

• chr19-727021-G-A
• rs201995410
• NM_002579.3:c.71G>A

Variant summary

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

The NM_002579.3(PALM):​c.71G>A​(p.Arg24Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,194,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R24W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: PALM NM_002579.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 2.63
• Publications: 2 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 (MetaRNN=0.045523226).

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.71G>A	p.Arg24Gln	missense	Exon 3 of 9	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.71G>A	p.Arg24Gln	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.71G>A	p.Arg24Gln	missense	Exon 3 of 9	ENSP00000341911.4	O75781-1
	PALM	ENST00000264560.11	TSL:4	c.71G>A	p.Arg24Gln	missense	Exon 3 of 8	ENSP00000264560.7	O75781-2
	PALM	ENST00000964891.1		c.71G>A	p.Arg24Gln	missense	Exon 3 of 8	ENSP00000634950.1

Frequencies

GnomAD3 genomes AF: 0.000529 AC: 76 AN: 143584 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000690

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000248

Gnomad FIN AF: 0.000326

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000977

Gnomad OTH AF: 0.00149

GnomAD2 exomes AF: 0.000416 AC: 61 AN: 146634 AF XY: 0.000484

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000963

Gnomad OTH exome AF: 0.000238

GnomAD4 exome AF: 0.00119 AC: 1249 AN: 1051104 Hom.: 0 Cov.: 30 AF XY: 0.00114 AC XY: 592 AN XY: 520318

African (AFR) AF: 0.00 AC: 0 AN: 22710

American (AMR) AF: 0.000174 AC: 5 AN: 28764

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15862

East Asian (EAS) AF: 0.00 AC: 0 AN: 14268

South Asian (SAS) AF: 0.000134 AC: 10 AN: 74738

European-Finnish (FIN) AF: 0.000529 AC: 15 AN: 28366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3800

European-Non Finnish (NFE) AF: 0.00144 AC: 1186 AN: 823730

Other (OTH) AF: 0.000849 AC: 33 AN: 38866

GnomAD4 genome AF: 0.000529 AC: 76 AN: 143728 Hom.: 0 Cov.: 30 AF XY: 0.000629 AC XY: 44 AN XY: 69956

African (AFR) AF: 0.000101 AC: 4 AN: 39754

American (AMR) AF: 0.0000689 AC: 1 AN: 14522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3354

East Asian (EAS) AF: 0.00 AC: 0 AN: 4170

South Asian (SAS) AF: 0.000247 AC: 1 AN: 4042

European-Finnish (FIN) AF: 0.000326 AC: 3 AN: 9192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000977 AC: 64 AN: 65500

Other (OTH) AF: 0.00147 AC: 3 AN: 2042

Alfa AF: 0.000836 Hom.: 0

Bravo AF: 0.000461

ESP6500AA AF: 0.000267 AC: 1

ESP6500EA AF: 0.00108 AC: 8

ExAC AF: 0.000202 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	atypical cerebral palsy (1)
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.058
Sift	Benign	0.073	T
Sift4G	Benign	0.14	T
Polyphen		0.88	P
Vest4		0.32
MVP		0.37
MPC		0.34
ClinPred		0.096	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.13
Mutation Taster		=95/5	polymorphism

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: rs201995410; hg19: chr19-727021;