Variant chr5-177489554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000393551.5(PDLIM7):c.646G>A(p.Gly216Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,610,658 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 15 hom., cov: 34)

Exomes 𝑓: 0.00083 ( 10 hom. )

Consequence

PDLIM7
ENST00000393551.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.35

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034395158).

BP6

Variant 5-177489554-C-T is Benign according to our data. Variant chr5-177489554-C-T is described in ClinVar as [Benign]. Clinvar id is 783626.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0072 (1097/152310) while in subpopulation AFR AF= 0.0238 (990/41568). AF 95% confidence interval is 0.0226. There are 15 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1097 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PDLIM7	NM_005451.5 linkuse as main transcript	c.708G>A	p.Pro236=	synonymous_variant	9/13	ENST00000355841.7
PDLIM7	NM_203352.3 linkuse as main transcript	c.606G>A	p.Pro202=	synonymous_variant	9/13
PDLIM7	NR_103804.2 linkuse as main transcript	n.995G>A		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.708G>A	p.Pro236=	synonymous_variant	9/13	1	NM_005451.5	P3	Q9NR12-1

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1093

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

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:

0.000220

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00183

AC:

441

AN:

241024

Hom.:

AF XY:

0.00134

AC XY:

176

AN XY:

131144

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000668

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000176

Gnomad OTH exome

AF:

0.000854

GnomAD4 exome

AF:

0.000832

AC:

1213

AN:

1458348

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

531

AN XY:

725396

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.00207

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.00191

GnomAD4 genome

AF:

0.00720

AC:

1097

AN:

152310

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00182

Hom.:

Bravo

AF:

0.00869

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0237

AC:

104

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.00224

AC:

270

Asia WGS

AF:

0.00144

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

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.4

DANN

Uncertain

0.99

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;N;N

PROVEAN

Benign

-0.75

REVEL

Benign

0.023

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.033

Polyphen

0.071

Vest4

0.18

MutPred

0.19

Gain of loop (P = 0.0502);

MVP

0.18

ClinPred

0.012

GERP RS

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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