19-726146-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_002579.3(PALM):​c.14C>T​(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,612,734 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. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: PALM NM_002579.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.89
• Publications: 3 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011496931).
• BP6: Variant 19-726146-C-T is Benign according to our data. Variant chr19-726146-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1981142.

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.14C>T	p.Ala5Val	missense	Exon 2 of 9	NP_002570.2	O75781-1
	PALM	NM_001040134.2		c.14C>T	p.Ala5Val	missense	Exon 2 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.14C>T	p.Ala5Val	missense	Exon 2 of 9	ENSP00000341911.4	O75781-1
	PALM	ENST00000264560.11	TSL:4	c.14C>T	p.Ala5Val	missense	Exon 2 of 8	ENSP00000264560.7	O75781-2
	PALM	ENST00000964891.1		c.14C>T	p.Ala5Val	missense	Exon 2 of 8	ENSP00000634950.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 250624 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000849 AC: 124 AN: 1460388 Hom.: 0 Cov.: 30 AF XY: 0.0000908 AC XY: 66 AN XY: 726600

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

American (AMR) AF: 0.0000895 AC: 4 AN: 44714

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86240

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52852

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

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111192

Other (OTH) AF: 0.000133 AC: 8 AN: 60350

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74502

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000503 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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	0.093
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.9
DANN	Benign	0.86
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		-1.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.019
Sift	Benign	0.60	T
Sift4G	Benign	0.85	T
Polyphen		0.0010	B
Vest4		0.14
MVP		0.19
MPC		0.14
ClinPred		0.0053	T
GERP RS		-4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.17
Mutation Taster		=93/7	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: rs372771354; hg19: chr19-726146; COSMIC: COSV52770735; COSMIC: COSV52770735;