Variant 1-99667734-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017734.5(PALMD):c.219C>A(p.His73Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,613,402 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 77 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 82 hom. )

Consequence

PALMD
NM_017734.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.647

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013098121).

BP6

Variant 1-99667734-C-A is Benign according to our data. Variant chr1-99667734-C-A is described in ClinVar as [Benign]. Clinvar id is 780771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PALMD	NM_017734.5 linkuse as main transcript	c.219C>A	p.His73Gln	missense_variant	3/8	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.219C>A	p.His73Gln	missense_variant	3/8	1	NM_017734.5	ENSP00000263174	P1	Q9NP74-1
PALMD	ENST00000605497.5 linkuse as main transcript	c.219C>A	p.His73Gln	missense_variant	3/7	1		ENSP00000473839
PALMD	ENST00000605613.1 linkuse as main transcript	n.155C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2726

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0621

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00492

AC:

1235

AN:

251018

Hom.:

AF XY:

0.00363

AC XY:

492

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.0670

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00198

AC:

2888

AN:

1461232

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

1306

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.0653

Gnomad4 AMR exome

AF:

0.00298

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.0181

AC:

2748

AN:

152170

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1309

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.00661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00311

Hom.:

Bravo

AF:

0.0200

ESP6500AA

AF:

0.0663

AC:

292

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00625

AC:

759

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0025

T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.84

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.93

N;.

REVEL

Benign

0.041

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.010

B;.

Vest4

0.22

MutPred

0.18

Gain of MoRF binding (P = 0.2697);Gain of MoRF binding (P = 0.2697);

MVP

0.16

MPC

0.079

ClinPred

0.0061

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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