13-32171040-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_023037.3(FRY):c.1921C>A(p.Arg641=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000711 in 1,608,456 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: FRY NM_023037.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.79

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 13-32171040-C-A is Benign according to our data. Variant chr13-32171040-C-A is described in ClinVar as [Benign]. Clinvar id is 708574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 572 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRY	NM_023037.3	c.1921C>A	p.Arg641=	synonymous_variant	18/61	ENST00000542859.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRY	ENST00000542859.6	c.1921C>A	p.Arg641=	synonymous_variant	18/61	5	NM_023037.3	A1
FRY	ENST00000647500.1	c.2056C>A	p.Arg686=	synonymous_variant	18/61
FRY	ENST00000642040.1	c.1921C>A	p.Arg641=	synonymous_variant	18/62			P4
FRY	ENST00000645780.1	c.1771C>A	p.Arg591=	synonymous_variant	19/62

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 572 AN: 151996 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000878 AC: 219 AN: 249410 Hom.: 2 AF XY: 0.000650 AC XY: 88 AN XY: 135336

Gnomad AFR exome AF: 0.0129

Gnomad AMR exome AF: 0.000492

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: 0.000165

GnomAD4 exome AF: 0.000391 AC: 570 AN: 1456342 Hom.: 3 Cov.: 30 AF XY: 0.000337 AC XY: 244 AN XY: 724930

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.000693

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000542

Gnomad4 OTH exome AF: 0.000664

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152114 Hom.: 3 Cov.: 32 AF XY: 0.00348 AC XY: 259 AN XY: 74364

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00143 Hom.: 3

Bravo AF: 0.00433

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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_noAF	Benign	-0.22
Cadd	Benign	14
Dann	Benign	0.77

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

Other links and lift over

dbSNP: rs116459776; hg19: chr13-32745177;