13-32135099-A-G

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.993A>G(p.Glu331=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000328 in 1,608,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: FRY NM_023037.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.03

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=-0.46).
• BP6: Variant 13-32135099-A-G is Benign according to our data. Variant chr13-32135099-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 784676.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRY	NM_023037.3	c.993A>G	p.Glu331=	synonymous_variant	10/61	ENST00000542859.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRY	ENST00000542859.6	c.993A>G	p.Glu331=	synonymous_variant	10/61	5	NM_023037.3	A1
FRY	ENST00000647500.1	c.1128A>G	p.Glu376=	synonymous_variant	10/61
FRY	ENST00000642040.1	c.993A>G	p.Glu331=	synonymous_variant	10/62			P4
FRY	ENST00000645780.1	c.843A>G	p.Glu281=	synonymous_variant	11/62

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000313 AC: 78 AN: 249332 Hom.: 0 AF XY: 0.000355 AC XY: 48 AN XY: 135288

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.000795

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000530

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000324 AC: 472 AN: 1456554 Hom.: 0 Cov.: 29 AF XY: 0.000352 AC XY: 255 AN XY: 725040

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000372

Gnomad4 OTH exome AF: 0.000299

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21 AN XY: 74376

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000410 Hom.: 0

Bravo AF: 0.000370

EpiCase AF: 0.000382

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	11
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs200632433; hg19: chr13-32709236;