13-32124369-T-C

Position:

• chr13-32124369-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023037.3(FRY):​c.548T>C​(p.Leu183Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FRY NM_023037.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.07

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRY	NM_023037.3	c.548T>C	p.Leu183Ser	missense_variant	5/61	ENST00000542859.6	NP_075463.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRY	ENST00000542859.6	c.548T>C	p.Leu183Ser	missense_variant	5/61	5	NM_023037.3	ENSP00000445043.2
FRY	ENST00000647500.1	c.683T>C	p.Leu228Ser	missense_variant	5/61			ENSP00000494761.1
FRY	ENST00000642040.1	c.548T>C	p.Leu183Ser	missense_variant	5/62			ENSP00000493189.1
FRY	ENST00000645780.1	c.398T>C	p.Leu133Ser	missense_variant	6/62			ENSP00000494080.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 03, 2024

The c.548T>C (p.L183S) alteration is located in exon 5 (coding exon 5) of the FRY gene. This alteration results from a T to C substitution at nucleotide position 548, causing the leucine (L) at amino acid position 183 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	.;.;.;T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.66	D;D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	.;.;.;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.7	.;.;.;D;.
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	.;.;.;D;.
Sift4G	Pathogenic	0.0010	.;.;.;D;D
Polyphen		1.0	.;.;.;.;D
Vest4		0.64, 0.77
MutPred		0.66		.;.;Loss of stability (P = 0.0482);Loss of stability (P = 0.0482);Loss of stability (P = 0.0482);
MVP		0.093
MPC		1.5
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.80
gMVP		0.83

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-32698506;