rs1064795975

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_024675.4(PALB2):​c.3421G>T​(p.Asp1141Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1141H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PALB2
NM_024675.4 missense

Scores

5
10
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.39
Variant links:
Genes affected
PALB2 (HGNC:26144): (partner and localizer of BRCA2) This gene encodes a protein that may function in tumor suppression. This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PALB2NM_024675.4 linkuse as main transcriptc.3421G>T p.Asp1141Tyr missense_variant 13/13 ENST00000261584.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PALB2ENST00000261584.9 linkuse as main transcriptc.3421G>T p.Asp1141Tyr missense_variant 13/131 NM_024675.4 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.081
T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.078
D
MetaRNN
Pathogenic
0.80
D;D
MetaSVM
Benign
-0.52
T
MutationAssessor
Uncertain
2.1
.;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-8.0
D;D
REVEL
Uncertain
0.48
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.74
MutPred
0.62
.;Gain of helix (P = 0.132);
MVP
0.78
MPC
0.38
ClinPred
1.0
D
GERP RS
4.8
Varity_R
0.95
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23614920; API