19-14053845-G-A

Position:

• chr19-14053845-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001145028.2(PALM3):​c.1827C>T​(p.Thr609Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00243 in 1,551,262 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (27 hom.)
• Consequence: PALM3 NM_001145028.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.13

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-14053845-G-A is Benign according to our data. Variant chr19-14053845-G-A is described in ClinVar as [Benign]. Clinvar id is 781460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.13 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1761/152160) while in subpopulation AFR AF= 0.0386 (1601/41492). AF 95% confidence interval is 0.037. There are 38 homozygotes in gnomad4. There are 820 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALM3	NM_001145028.2	c.1827C>T	p.Thr609Thr	synonymous_variant	7/7	ENST00000669674.2	NP_001138500.2
PALM3	NM_001367327.1	c.1629C>T	p.Thr543Thr	synonymous_variant	5/5		NP_001354256.1
PALM3	XM_047438763.1	c.1746C>T	p.Thr582Thr	synonymous_variant	6/6		XP_047294719.1
PALM3	XM_047438764.1	c.1629C>T	p.Thr543Thr	synonymous_variant	5/5		XP_047294720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALM3	ENST00000669674.2	c.1827C>T	p.Thr609Thr	synonymous_variant	7/7		NM_001145028.2	ENSP00000499271.1
PALM3	ENST00000340790.9	c.1782C>T	p.Thr594Thr	synonymous_variant	6/6	5		ENSP00000344996.3
PALM3	ENST00000661591.1	c.1707C>T	p.Thr569Thr	synonymous_variant	4/4			ENSP00000499248.1
PALM3	ENST00000589048.2	c.1629C>T	p.Thr543Thr	synonymous_variant	5/5	3		ENSP00000465701.2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1758 AN: 152044 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.00719

GnomAD3 exomes AF: 0.00337 AC: 519 AN: 153796 Hom.: 7 AF XY: 0.00299 AC XY: 244 AN XY: 81556

Gnomad AFR exome AF: 0.0438

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00747

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000879

Gnomad FIN exome AF: 0.000262

Gnomad NFE exome AF: 0.000454

Gnomad OTH exome AF: 0.00162

GnomAD4 exome AF: 0.00143 AC: 2002 AN: 1399102 Hom.: 27 Cov.: 31 AF XY: 0.00130 AC XY: 898 AN XY: 690074

Gnomad4 AFR exome AF: 0.0404

Gnomad4 AMR exome AF: 0.00297

Gnomad4 ASJ exome AF: 0.00740

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000884

Gnomad4 FIN exome AF: 0.000325

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0116 AC: 1761 AN: 152160 Hom.: 38 Cov.: 32 AF XY: 0.0110 AC XY: 820 AN XY: 74386

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00807

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00435 Hom.: 6

Bravo AF: 0.0135

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.77

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: rs80123117; hg19: chr19-14164657;