rs80123117

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-14053845-G-A
• chr19-14053845-G-T

Variant summary

Our verdict is Benign. The variant received -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
• 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

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

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

GnomAD2 exomes AF: 0.00337 AC: 519 AN: 153796 AF XY: 0.00299

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 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

African (AFR) AF: 0.0404 AC: 1275 AN: 31588

American (AMR) AF: 0.00297 AC: 106 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00740 AC: 186 AN: 25128

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

South Asian (SAS) AF: 0.0000884 AC: 7 AN: 79222

European-Finnish (FIN) AF: 0.000325 AC: 16 AN: 49284

Middle Eastern (MID) AF: 0.00246 AC: 14 AN: 5694

European-Non Finnish (NFE) AF: 0.000179 AC: 193 AN: 1078780

Other (OTH) AF: 0.00353 AC: 205 AN: 58000

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

African (AFR) AF: 0.0386 AC: 1601 AN: 41492

American (AMR) AF: 0.00569 AC: 87 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67978

Other (OTH) AF: 0.00712 AC: 15 AN: 2108

Alfa AF: 0.00955 Hom.: 13

Bravo AF: 0.0135

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.0
DANN	Benign	0.77
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs80123117; hg19: chr19-14164657;