Variant chr1-99689132-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017734.5(PALMD):c.872C>T(p.Thr291Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

PALMD
NM_017734.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600

Variant links:

Genes affected

PALMD (HGNC:15846): (palmdelphin) Predicted to be involved in regulation of cell shape. Predicted to be located in dendrite. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PALMD links:

PALMD (HGNC:):

PALMD links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047729135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALMD	NM_017734.5 linkuse as main transcript	c.872C>T	p.Thr291Ile	missense_variant	7/8	ENST00000263174.9	NP_060204.1	Q9NP74-1A0A0S2Z5E7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PALMD	ENST00000263174.9 linkuse as main transcript	c.872C>T	p.Thr291Ile	missense_variant	7/8	1	NM_017734.5	ENSP00000263174.4	Q9NP74-1
PALMD	ENST00000605497.5 linkuse as main transcript	c.872C>T	p.Thr291Ile	missense_variant	7/7	1		ENSP00000473839.1	S4R313
PALMD	ENST00000496843.1 linkuse as main transcript	n.4031C>T		non_coding_transcript_exon_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151900

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.872C>T (p.T291I) alteration is located in exon 7 (coding exon 7) of the PALMD gene. This alteration results from a C to T substitution at nucleotide position 872, causing the threonine (T) at amino acid position 291 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.0069

T;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.90

L;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.10

N;.;.

REVEL

Benign

0.049

Sift

Benign

0.50

T;.;.

Sift4G

Benign

0.23

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.088

MutPred

0.49

Loss of disorder (P = 0.0542);Loss of disorder (P = 0.0542);.;

MVP

0.26

MPC

0.032

ClinPred

0.034

GERP RS

3.1

Varity_R

0.070

gMVP

0.25

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over