rs61731845

chr19-14054912-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001145028.2(PALM3):c.760G>A(p.Glu254Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,549,352 control chromosomes in the GnomAD database, including 78 homozygotes. 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: 𝑓 0.013 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (38 hom.)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.926

Genes affected

PALM3 (HGNC:33274): (paralemmin 3) Predicted to enable ATP binding activity. Involved in Toll signaling pathway; negative regulation of cytokine-mediated signaling pathway; and response to lipopolysaccharide. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033938289).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2020/152316) while in subpopulation AFR AF= 0.0451 (1874/41564). AF 95% confidence interval is 0.0434. There are 40 homozygotes in gnomad4. There are 972 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALM3	NM_001145028.2	c.760G>A	p.Glu254Lys	missense_variant	7/7	ENST00000669674.2
PALM3	NM_001367327.1	c.562G>A	p.Glu188Lys	missense_variant	5/5
PALM3	XM_047438763.1	c.679G>A	p.Glu227Lys	missense_variant	6/6
PALM3	XM_047438764.1	c.562G>A	p.Glu188Lys	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALM3	ENST00000669674.2	c.760G>A	p.Glu254Lys	missense_variant	7/7		NM_001145028.2	A2
PALM3	ENST00000340790.9	c.715G>A	p.Glu239Lys	missense_variant	6/6	5		P4
PALM3	ENST00000661591.1	c.640G>A	p.Glu214Lys	missense_variant	4/4			A2
PALM3	ENST00000589048.2	c.562G>A	p.Glu188Lys	missense_variant	5/5	3		A2

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2011 AN: 152198 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00332 AC: 512 AN: 154318 Hom.: 13 AF XY: 0.00256 AC XY: 210 AN XY: 81978

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000440

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.00687

GnomAD4 exome AF: 0.00153 AC: 2135 AN: 1397036 Hom.: 38 Cov.: 35 AF XY: 0.00133 AC XY: 918 AN XY: 689202

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.00443

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000560

Gnomad4 SAS exome AF: 0.000101

Gnomad4 FIN exome AF: 0.0000425

Gnomad4 NFE exome AF: 0.000205

Gnomad4 OTH exome AF: 0.00355

GnomAD4 genome AF: 0.0133 AC: 2020 AN: 152316 Hom.: 40 Cov.: 32 AF XY: 0.0131 AC XY: 972 AN XY: 74480

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.00679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00254 Hom.: 10

Bravo AF: 0.0152

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0405 AC: 56

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00414 AC: 129

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
Cadd	Uncertain	23
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.013	T;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.83	T;.
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.94	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;.
REVEL	Benign	0.080
Sift	Uncertain	0.0050	D;.
Sift4G	Benign	0.10	T;D
Polyphen		1.0	D;.
Vest4		0.41
MVP		0.061
ClinPred		0.032	T
GERP RS		3.7
Varity_R		0.24
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs61731845; hg19: chr19-14165724;