19-726146-C-G

Variant names:

• chr19-726146-C-G
• rs372771354
• NM_002579.3:c.14C>G

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.14C>G​(p.Ala5Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PALM NM_002579.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• 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 (MetaRNN=0.03632313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM	NM_002579.3	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 9	ENST00000338448.10	NP_002570.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM	ENST00000338448.10	c.14C>G	p.Ala5Gly	missense_variant	Exon 2 of 9	1	NM_002579.3	ENSP00000341911.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460392 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726602

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111196

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.84
DEOGEN2	Benign	0.073	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.49	T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N;N;.
PhyloP100		-1.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.5	N;N;.
REVEL	Benign	0.025
Sift	Benign	0.13	T;D;.
Sift4G	Benign	0.21	T;T;.
Polyphen		0.0010	B;B;.
Vest4		0.20
MutPred		0.10		Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.21
MPC		0.14
ClinPred		0.021	T
GERP RS		-4.3
Varity_R		0.090
gMVP		0.18
Mutation Taster		=92/8	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: rs372771354; hg19: chr19-726146;