13-32136383-G-C

Variant names:

• chr13-32136383-G-C
• rs7331540
• NM_023037.3:c.1078-488G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_023037.3(FRY):​c.1078-488G>C variant causes a intron change. The variant allele was found at a frequency of 0.489 in 151,930 control chromosomes in the GnomAD database, including 18,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18779 hom., cov: 32)
• Consequence: FRY NM_023037.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023037.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	NM_023037.3	MANE Select	c.1078-488G>C		intron	N/A	NP_075463.2
	FRY	NM_001411012.1		c.1078-488G>C		intron	N/A	NP_001397941.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	ENST00000542859.6	TSL:5 MANE Select	c.1078-488G>C		intron	N/A	ENSP00000445043.2
	FRY	ENST00000647500.1		c.1213-488G>C		intron	N/A	ENSP00000494761.1
	FRY	ENST00000642040.1		c.1078-488G>C		intron	N/A	ENSP00000493189.1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74247 AN: 151814 Hom.: 18765 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.482

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.489 AC: 74296 AN: 151930 Hom.: 18779 Cov.: 32 AF XY: 0.496 AC XY: 36798 AN XY: 74224

African (AFR) AF: 0.568 AC: 23523 AN: 41424

American (AMR) AF: 0.476 AC: 7262 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3466

East Asian (EAS) AF: 0.813 AC: 4202 AN: 5166

South Asian (SAS) AF: 0.618 AC: 2979 AN: 4818

European-Finnish (FIN) AF: 0.460 AC: 4860 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28461 AN: 67934

Other (OTH) AF: 0.481 AC: 1011 AN: 2104

Alfa AF: 0.275 Hom.: 601

Bravo AF: 0.493

Asia WGS AF: 0.656 AC: 2282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.79
PhyloP100		4.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7331540; hg19: chr13-32710520;