19-14053613-C-G

Variant names:

• chr19-14053613-C-G
• NM_001145028.2:c.2059G>C

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.2059G>C​(p.Val687Leu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.379
• Publications: 0 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=0.1864706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145028.2. 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
	PALM3	NM_001145028.2	MANE Select	c.2059G>C	p.Val687Leu	missense	Exon 7 of 7	NP_001138500.2	A0A590UJ36
	PALM3	NM_001367327.1		c.1861G>C	p.Val621Leu	missense	Exon 5 of 5	NP_001354256.1	K7EKN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PALM3	ENST00000669674.2	MANE Select	c.2059G>C	p.Val687Leu	missense	Exon 7 of 7	ENSP00000499271.1	A0A590UJ36
	PALM3	ENST00000661591.1		c.1939G>C	p.Val647Leu	missense	Exon 4 of 4	ENSP00000499248.1	A0A590UJ23
	PALM3	ENST00000589048.2	TSL:3	c.1861G>C	p.Val621Leu	missense	Exon 5 of 5	ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		0.38
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.034	D
Polyphen		0.75	P
Vest4		0.28
MutPred		0.32		Loss of sheet (P = 0.0126)
MVP		0.040
ClinPred		0.24	T
GERP RS		2.5
Varity_R		0.14
gMVP		0.16
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr19-14164425;