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19-14053845-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001145028.2(PALM3):c.1827C>T(p.Thr609=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.13
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.13 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PALM3NM_001145028.2 linkuse as main transcriptc.1827C>T p.Thr609= synonymous_variant 7/7 ENST00000669674.2
PALM3NM_001367327.1 linkuse as main transcriptc.1629C>T p.Thr543= synonymous_variant 5/5
PALM3XM_047438763.1 linkuse as main transcriptc.1746C>T p.Thr582= synonymous_variant 6/6
PALM3XM_047438764.1 linkuse as main transcriptc.1629C>T p.Thr543= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PALM3ENST00000669674.2 linkuse as main transcriptc.1827C>T p.Thr609= synonymous_variant 7/7 NM_001145028.2 A2
PALM3ENST00000340790.9 linkuse as main transcriptc.1782C>T p.Thr594= synonymous_variant 6/65 P4
PALM3ENST00000661591.1 linkuse as main transcriptc.1707C>T p.Thr569= synonymous_variant 4/4 A2
PALM3ENST00000589048.2 linkuse as main transcriptc.1629C>T p.Thr543= synonymous_variant 5/53 A2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0116
AC:
1758
AN:
152044
Hom.:
37
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0116
AC:
1761
AN:
152160
Hom.:
38
Cov.:
32
AF XY:
0.0110
AC XY:
820
AN XY:
74386
show subpopulations
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:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs80123117; hg19: chr19-14164657; API