19-14053845-G-T

Variant names:

• chr19-14053845-G-T
• rs80123117
• NM_001145028.2:c.1827C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145028.2(PALM3):​c.1827C>A​(p.Thr609Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T609T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PALM3 NM_001145028.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.

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.1827C>A	p.Thr609Thr	synonymous	Exon 7 of 7	NP_001138500.2	A0A590UJ36
	PALM3	NM_001367327.1		c.1629C>A	p.Thr543Thr	synonymous	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.1827C>A	p.Thr609Thr	synonymous	Exon 7 of 7	ENSP00000499271.1	A0A590UJ36
	PALM3	ENST00000661591.1		c.1707C>A	p.Thr569Thr	synonymous	Exon 4 of 4	ENSP00000499248.1	A0A590UJ23
	PALM3	ENST00000589048.2	TSL:3	c.1629C>A	p.Thr543Thr	synonymous	Exon 5 of 5	ENSP00000465701.2	K7EKN5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399102 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690074

African (AFR) AF: 0.00 AC: 0 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25128

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078780

Other (OTH) AF: 0.0000172 AC: 1 AN: 58000

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.23
DANN	Benign	0.79
PhyloP100		-1.1

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: rs80123117; hg19: chr19-14164657;