19-14053613-C-G

Position:

• chr19-14053613-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/20 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

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1864706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.2059G>C	p.Val687Leu	missense_variant	7/7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.1861G>C	p.Val621Leu	missense_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1	c.1978G>C	p.Val660Leu	missense_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1	c.1861G>C	p.Val621Leu	missense_variant	5/5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM3	ENST00000669674.2	c.2059G>C	p.Val687Leu	missense_variant	7/7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.2014G>C	p.Val672Leu	missense_variant	6/6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.1939G>C	p.Val647Leu	missense_variant	4/4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.1861G>C	p.Val621Leu	missense_variant	5/5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.2014G>C (p.V672L) alteration is located in exon 6 (coding exon 6) of the PALM3 gene. This alteration results from a G to C substitution at nucleotide position 2014, causing the valine (V) at amino acid position 672 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-14164425;