19-14054081-C-G

Variant names:

• chr19-14054081-C-G
• rs1327166701
• NM_001145028.2:c.1591G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145028.2(PALM3):​c.1591G>C​(p.Glu531Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. E531K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0547795).

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.1591G>C	p.Glu531Gln	missense	Exon 7 of 7	NP_001138500.2	A0A590UJ36
	PALM3	NM_001367327.1		c.1393G>C	p.Glu465Gln	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.1591G>C	p.Glu531Gln	missense	Exon 7 of 7	ENSP00000499271.1	A0A590UJ36
	PALM3	ENST00000661591.1		c.1471G>C	p.Glu491Gln	missense	Exon 4 of 4	ENSP00000499248.1	A0A590UJ23
	PALM3	ENST00000589048.2	TSL:3	c.1393G>C	p.Glu465Gln	missense	Exon 5 of 5	ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399606 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690304

African (AFR) AF: 0.00 AC: 0 AN: 31570

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35742

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079010

Other (OTH) AF: 0.00 AC: 0 AN: 58060

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.77
DANN	Benign	0.86
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.0020
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.0050
Sift	Benign	0.26	T
Sift4G	Benign	0.15	T
Polyphen		0.0020	B
Vest4		0.029
MutPred		0.21		Loss of helix (P = 0.0626)
MVP		0.014
ClinPred		0.045	T
GERP RS		-0.086
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.057
gMVP		0.022
Mutation Taster		=99/1	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: rs1327166701; hg19: chr19-14164893;