rs1202322773

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-14054026-G-A
• chr19-14054026-G-C
• chr19-14054026-G-T

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.1646C>T​(p.Thr549Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,551,424 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: PALM3 NM_001145028.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.495
• Publications: 1 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=0.039499998).

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.1646C>T	p.Thr549Met	missense	Exon 7 of 7	NP_001138500.2	A0A590UJ36
	PALM3	NM_001367327.1		c.1448C>T	p.Thr483Met	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.1646C>T	p.Thr549Met	missense	Exon 7 of 7	ENSP00000499271.1	A0A590UJ36
	PALM3	ENST00000661591.1		c.1526C>T	p.Thr509Met	missense	Exon 4 of 4	ENSP00000499248.1	A0A590UJ23
	PALM3	ENST00000589048.2	TSL:3	c.1448C>T	p.Thr483Met	missense	Exon 5 of 5	ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151896 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000968

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

GnomAD2 exomes AF: 0.0000129 AC: 2 AN: 154990 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000332

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000207 AC: 29 AN: 1399528 Hom.: 0 Cov.: 31 AF XY: 0.0000130 AC XY: 9 AN XY: 690290

African (AFR) AF: 0.0000633 AC: 2 AN: 31598

American (AMR) AF: 0.0000560 AC: 2 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000222 AC: 24 AN: 1079002

Other (OTH) AF: 0.0000172 AC: 1 AN: 58026

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151896 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74192

African (AFR) AF: 0.0000968 AC: 4 AN: 41318

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000189

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	0.084
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.5
DANN	Benign	0.90
DEOGEN2	Benign	0.00070	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.49
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.0060
Sift	Benign	0.044	D
Sift4G	Benign	0.10	T
Polyphen		0.021	B
Vest4		0.081
MutPred		0.15		Loss of phosphorylation at T534 (P = 0.0202)
MVP		0.014
ClinPred		0.052	T
GERP RS		-5.7
Varity_R		0.019
gMVP		0.030
Mutation Taster		=89/11	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: rs1202322773; hg19: chr19-14164838;