13-32078841-C-T

Variant names:

• chr13-32078841-C-T
• rs184309723
• NM_023037.3:c.78C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_023037.3(FRY):​c.78C>T​(p.Pro26Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000271 in 1,613,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: FRY NM_023037.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.328
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 13-32078841-C-T is Benign according to our data. Variant chr13-32078841-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 720490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.328 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	NM_023037.3	MANE Select	c.78C>T	p.Pro26Pro	synonymous	Exon 2 of 61	NP_075463.2	Q5TBA9
	FRY	NM_001411012.1		c.78C>T	p.Pro26Pro	synonymous	Exon 2 of 62	NP_001397941.1	A0A286YFA9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRY	ENST00000542859.6	TSL:5 MANE Select	c.78C>T	p.Pro26Pro	synonymous	Exon 2 of 61	ENSP00000445043.2	Q5TBA9
	FRY	ENST00000645780.1		c.-73C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 62	ENSP00000494080.1	A0A2R8YCY2
	FRY	ENST00000647500.1		c.213C>T	p.Pro71Pro	synonymous	Exon 2 of 61	ENSP00000494761.1	A0A2R8Y5V8

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 224 AN: 152148 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00516

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000345 AC: 86 AN: 249512 AF XY: 0.000296

Gnomad AFR exome AF: 0.00497

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000145 AC: 212 AN: 1461336 Hom.: 0 Cov.: 31 AF XY: 0.000133 AC XY: 97 AN XY: 727028

African (AFR) AF: 0.00535 AC: 179 AN: 33460

American (AMR) AF: 0.000134 AC: 6 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5728

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111564

Other (OTH) AF: 0.000182 AC: 11 AN: 60378

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152266 Hom.: 1 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74434

African (AFR) AF: 0.00517 AC: 215 AN: 41562

American (AMR) AF: 0.000261 AC: 4 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000806 Hom.: 0

Bravo AF: 0.00171

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		-0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs184309723; hg19: chr13-32652978;