chr19-14055064-G-C

Variant names:

• chr19-14055064-G-C
• rs201934041
• NM_001145028.2:c.608C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145028.2(PALM3):​c.608C>G​(p.Pro203Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P203L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09188625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.608C>G	p.Pro203Arg	missense_variant	Exon 7 of 7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.410C>G	p.Pro137Arg	missense_variant	Exon 5 of 5		NP_001354256.1
PALM3	XM_047438763.1	c.527C>G	p.Pro176Arg	missense_variant	Exon 6 of 6		XP_047294719.1
PALM3	XM_047438764.1	c.410C>G	p.Pro137Arg	missense_variant	Exon 5 of 5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PALM3	ENST00000669674.2	c.608C>G	p.Pro203Arg	missense_variant	Exon 7 of 7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.563C>G	p.Pro188Arg	missense_variant	Exon 6 of 6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.488C>G	p.Pro163Arg	missense_variant	Exon 4 of 4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.410C>G	p.Pro137Arg	missense_variant	Exon 5 of 5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000129 AC: 2 AN: 154738 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000184

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399266 Hom.: 0 Cov.: 35 AF XY: 0.00000145 AC XY: 1 AN XY: 690150

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078932

Other (OTH) AF: 0.00 AC: 0 AN: 58008

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.67	T;.
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;.
PhyloP100		0.27
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.097
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.014	D;T
Polyphen		0.99	D;.
Vest4		0.14
MutPred		0.17		Loss of glycosylation at S189 (P = 0.0766);.;
MVP		0.24
ClinPred		0.30	T
GERP RS		-2.1
Varity_R		0.25
gMVP		0.083
Mutation Taster		=100/0	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: rs201934041; hg19: chr19-14165876;