19-14054026-G-C

Variant names:

• chr19-14054026-G-C
• rs1202322773
• NM_001145028.2:c.1646C>G

Variant summary

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

The NM_001145028.2(PALM3):​c.1646C>G​(p.Thr549Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,551,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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=0.0499759).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.1646C>G	p.Thr549Arg	missense_variant	Exon 7 of 7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.1448C>G	p.Thr483Arg	missense_variant	Exon 5 of 5		NP_001354256.1
PALM3	XM_047438763.1	c.1565C>G	p.Thr522Arg	missense_variant	Exon 6 of 6		XP_047294719.1
PALM3	XM_047438764.1	c.1448C>G	p.Thr483Arg	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.1646C>G	p.Thr549Arg	missense_variant	Exon 7 of 7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.1601C>G	p.Thr534Arg	missense_variant	Exon 6 of 6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.1526C>G	p.Thr509Arg	missense_variant	Exon 4 of 4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.1448C>G	p.Thr483Arg	missense_variant	Exon 5 of 5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151896 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399528 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 690290

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151896 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74192

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.055
DANN	Benign	0.74
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.0070
Sift	Uncertain	0.024	D
Sift4G	Benign	0.091	T
Polyphen		0.20	B
Vest4		0.066
MutPred		0.20		Loss of phosphorylation at T534 (P = 0.0202);
MVP		0.014
ClinPred		0.14	T
GERP RS		-5.7
Varity_R		0.10
gMVP		0.036

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: rs1202322773; hg19: chr19-14164838;