NM_002579.3:c.77C>G

Variant names:

• chr19-727027-C-G
• rs200597947
• NM_002579.3:c.77C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002579.3(PALM):​c.77C>G​(p.Ala26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.000017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PALM NM_002579.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0055473447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM	NM_002579.3	c.77C>G	p.Ala26Gly	missense_variant	Exon 3 of 9	ENST00000338448.10	NP_002570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10	c.77C>G	p.Ala26Gly	missense_variant	Exon 3 of 9	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00168 AC: 235 AN: 139642 Hom.: 0 AF XY: 0.00109 AC XY: 82 AN XY: 75074

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.0000823

Gnomad ASJ exome AF: 0.000394

Gnomad EAS exome AF: 0.00178

Gnomad SAS exome AF: 0.0000905

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00141

Gnomad OTH exome AF: 0.00122

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000170 AC: 20 AN: 1178574 Hom.: 0 Cov.: 33 AF XY: 0.0000222 AC XY: 13 AN XY: 585404

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000197

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000266

Gnomad4 FIN exome AF: 0.000297

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000633

GnomAD4 genome Cov.: 30

ExAC AF: 0.00620 AC: 346

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.86	D;T
MetaRNN	Benign	0.0055	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.035
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.45	P;P
Vest4		0.26
MVP		0.32
MPC		0.15
ClinPred		0.041	T
GERP RS		2.8
Varity_R		0.21
gMVP		0.093

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

Publications

LitVar

Other links and lift over

dbSNP: rs200597947; hg19: chr19-727027; COSMIC: COSV52768579; COSMIC: COSV52768579;