Variant 1-99686783-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017734.5(PALMD):c.359T>G(p.Ile120Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000777 in 1,543,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

PALMD
NM_017734.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALMD	NM_017734.5 linkuse as main transcript	c.359T>G	p.Ile120Ser	missense_variant	4/8	ENST00000263174.9	NP_060204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PALMD	ENST00000263174.9 linkuse as main transcript	c.359T>G	p.Ile120Ser	missense_variant	4/8	1	NM_017734.5	ENSP00000263174	P1	Q9NP74-1
PALMD	ENST00000605497.5 linkuse as main transcript	c.359T>G	p.Ile120Ser	missense_variant	4/7	1		ENSP00000473839
PALMD	ENST00000496843.1 linkuse as main transcript	n.3518T>G		non_coding_transcript_exon_variant	1/5	1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000328

AC:

AN:

244000

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

131880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000790

AC:

AN:

1391704

Hom.:

Cov.:

AF XY:

0.00000431

AC XY:

AN XY:

696328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

Aug 30, 2022

The c.359T>G (p.I120S) alteration is located in exon 4 (coding exon 4) of the PALMD gene. This alteration results from a T to G substitution at nucleotide position 359, causing the isoleucine (I) at amino acid position 120 to be replaced by a serine (S). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.7

D;.;.

REVEL

Benign

0.28

Sift

Uncertain

0.027

D;.;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.83

MutPred

0.48

Gain of phosphorylation at I120 (P = 0.0051);Gain of phosphorylation at I120 (P = 0.0051);.;

MVP

0.81

MPC

0.27

ClinPred

0.65

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.55

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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