NM_023037.3:c.1233T>C

Variant names:

• chr13-32147335-T-C
• rs1593667198
• NM_023037.3:c.1233T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_023037.3(FRY):​c.1233T>C​(p.Leu411Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRY NM_023037.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.41
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 13-32147335-T-C is Benign according to our data. Variant chr13-32147335-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 747924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 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.1233T>C	p.Leu411Leu	synonymous	Exon 12 of 61	NP_075463.2	Q5TBA9
	FRY	NM_001411012.1		c.1233T>C	p.Leu411Leu	synonymous	Exon 12 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.1233T>C	p.Leu411Leu	synonymous	Exon 12 of 61	ENSP00000445043.2	Q5TBA9
	FRY	ENST00000647500.1		c.1368T>C	p.Leu456Leu	synonymous	Exon 12 of 61	ENSP00000494761.1	A0A2R8Y5V8
	FRY	ENST00000642040.1		c.1233T>C	p.Leu411Leu	synonymous	Exon 12 of 62	ENSP00000493189.1	A0A286YFA9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-2.4

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: rs1593667198; hg19: chr13-32721472;