Variant 5-177489464-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000393551.5(PDLIM7):c.736C>T(p.Arg246Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000815 in 1,605,022 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 4 hom. )

Consequence

PDLIM7
ENST00000393551.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.66

Variant links:

Genes affected

PDLIM7 (HGNC:22958): (PDZ and LIM domain 7) The protein encoded by this gene is representative of a family of proteins composed of conserved PDZ and LIM domains. LIM domains are proposed to function in protein-protein recognition in a variety of contexts including gene transcription and development and in cytoskeletal interaction. The LIM domains of this protein bind to protein kinases, whereas the PDZ domain binds to actin filaments. The gene product is involved in the assembly of an actin filament-associated complex essential for transmission of ret/ptc2 mitogenic signaling. The biological function is likely to be that of an adapter, with the PDZ domain localizing the LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

PDLIM7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039896965).

BP6

Variant 5-177489464-G-A is Benign according to our data. Variant chr5-177489464-G-A is described in ClinVar as [Benign]. Clinvar id is 724049.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDLIM7	NM_005451.5 linkuse as main transcript	c.798C>T	p.Ala266=	synonymous_variant	9/13	ENST00000355841.7
PDLIM7	NM_203352.3 linkuse as main transcript	c.696C>T	p.Ala232=	synonymous_variant	9/13
PDLIM7	NR_103804.2 linkuse as main transcript	n.1085C>T		non_coding_transcript_exon_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDLIM7	ENST00000355841.7 linkuse as main transcript	c.798C>T	p.Ala266=	synonymous_variant	9/13	1	NM_005451.5	P3	Q9NR12-1

Frequencies

GnomAD3 genomes

AF:

0.000512

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00102

AC:

234

AN:

230344

Hom.:

AF XY:

0.00138

AC XY:

173

AN XY:

125200

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00573

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000590

Gnomad OTH exome

AF:

0.000533

GnomAD4 exome

AF:

0.000846

AC:

1229

AN:

1452686

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

762

AN XY:

721814

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00527

Gnomad4 FIN exome

AF:

0.000136

Gnomad4 NFE exome

AF:

0.000649

Gnomad4 OTH exome

AF:

0.000600

GnomAD4 genome

AF:

0.000519

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000550

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000459

Hom.:

Bravo

AF:

0.000461

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000853

AC:

103

Asia WGS

AF:

0.00260

AC:

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 submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.11

DANN

Benign

0.76

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

-0.63

REVEL

Benign

0.022

Sift

Uncertain

0.012

Sift4G

Uncertain

0.024

Polyphen

0.0

Vest4

0.18

MVP

0.24

ClinPred

0.017

GERP RS

-7.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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