19-14054366-G-A

Variant names:

• chr19-14054366-G-A
• NM_001145028.2:c.1306C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145028.2(PALM3):​c.1306C>T​(p.Pro436Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.110

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054735273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.1306C>T	p.Pro436Ser	missense_variant	Exon 7 of 7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.1108C>T	p.Pro370Ser	missense_variant	Exon 5 of 5		NP_001354256.1
PALM3	XM_047438763.1	c.1225C>T	p.Pro409Ser	missense_variant	Exon 6 of 6		XP_047294719.1
PALM3	XM_047438764.1	c.1108C>T	p.Pro370Ser	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.1306C>T	p.Pro436Ser	missense_variant	Exon 7 of 7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.1261C>T	p.Pro421Ser	missense_variant	Exon 6 of 6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.1186C>T	p.Pro396Ser	missense_variant	Exon 4 of 4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.1108C>T	p.Pro370Ser	missense_variant	Exon 5 of 5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1261C>T (p.P421S) alteration is located in exon 6 (coding exon 6) of the PALM3 gene. This alteration results from a C to T substitution at nucleotide position 1261, causing the proline (P) at amino acid position 421 to be replaced by a serine (S). 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	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.8
DANN	Benign	0.67
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.0070
Sift	Benign	0.11	T
Sift4G	Benign	0.15	T
Polyphen		0.017	B
Vest4		0.035
MutPred		0.27		Gain of phosphorylation at P421 (P = 0.0077);
MVP		0.030
ClinPred		0.060	T
GERP RS		2.0
Varity_R		0.050
gMVP		0.031

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-14165178;