Variant 13-32171259-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_023037.3(FRY):c.2140A>G(p.Arg714Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,611,188 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00028 ( 4 hom. )

Consequence

FRY
NM_023037.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

FRY (HGNC:20367): (FRY microtubule binding protein) Predicted to enable enzyme inhibitor activity. Predicted to be involved in cell morphogenesis and neuron projection development. Predicted to be located in microtubule organizing center and spindle pole. Predicted to be active in cell cortex and site of polarized growth. [provided by Alliance of Genome Resources, Apr 2022]

FRY links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, FRY

BP4

Computational evidence support a benign effect (MetaRNN=0.005289942).

BP6

Variant 13-32171259-A-G is Benign according to our data. Variant chr13-32171259-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 785443.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 408 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRY	NM_023037.3 linkuse as main transcript	c.2140A>G	p.Arg714Gly	missense_variant	18/61	ENST00000542859.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FRY	ENST00000542859.6 linkuse as main transcript	c.2140A>G	p.Arg714Gly	missense_variant	18/61	5	NM_023037.3	A1
FRY	ENST00000647500.1 linkuse as main transcript	c.2275A>G	p.Arg759Gly	missense_variant	18/61
FRY	ENST00000642040.1 linkuse as main transcript	c.2140A>G	p.Arg714Gly	missense_variant	18/62			P4
FRY	ENST00000645780.1 linkuse as main transcript	c.1990A>G	p.Arg664Gly	missense_variant	19/62

Frequencies

GnomAD3 genomes

AF:

0.00270

AC:

408

AN:

151344

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00960

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000417

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.000588

AC:

146

AN:

248470

Hom.:

AF XY:

0.000400

AC XY:

AN XY:

134878

show subpopulations

Gnomad AFR exome

AF:

0.00886

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000284

AC:

415

AN:

1459740

Hom.:

Cov.:

AF XY:

0.000233

AC XY:

169

AN XY:

726366

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.000514

GnomAD4 genome

AF:

0.00269

AC:

408

AN:

151448

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

208

AN XY:

73978

show subpopulations

Gnomad4 AFR

AF:

0.00958

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.0232

Hom.:

2354

Bravo

AF:

0.00300

ESP6500AA

AF:

0.0101

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000728

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 24, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D;D;D

MetaRNN

Benign

0.0053

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.50

Polyphen

0.0020

.;.;.;.;B

Vest4

0.51, 0.62

MVP

0.49

MPC

0.52

ClinPred

0.012

GERP RS

0.74

Varity_R

0.20

gMVP

0.57

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