Variant 13-32171022-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_023037.3(FRY):c.1903C>A(p.His635Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FRY
NM_023037.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.79

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 Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, FRY

PP3

MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRY	NM_023037.3 linkuse as main transcript	c.1903C>A	p.His635Asn	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.1903C>A	p.His635Asn	missense_variant	18/61	5	NM_023037.3	A1
FRY	ENST00000647500.1 linkuse as main transcript	c.2038C>A	p.His680Asn	missense_variant	18/61
FRY	ENST00000642040.1 linkuse as main transcript	c.1903C>A	p.His635Asn	missense_variant	18/62			P4
FRY	ENST00000645780.1 linkuse as main transcript	c.1753C>A	p.His585Asn	missense_variant	19/62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249386

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

Oct 13, 2023

The c.1903C>A (p.H635N) alteration is located in exon 18 (coding exon 18) of the FRY gene. This alteration results from a C to A substitution at nucleotide position 1903, causing the histidine (H) at amino acid position 635 to be replaced by an asparagine (N). 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

0.96

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

Cadd

Uncertain

Dann

Uncertain

0.99

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.85

D;D;D;D;D

MetaSVM

Uncertain

0.044

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

Polyphen

1.0

.;.;.;.;D

Vest4

0.70, 0.91

MutPred

0.66

.;.;Loss of stability (P = 0.0542);Loss of stability (P = 0.0542);Loss of stability (P = 0.0542);

MVP

0.64

MPC

1.3

ClinPred

1.0

GERP RS

5.9

Varity_R

0.86

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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