13-32078842-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_023037.3(FRY):c.79G>A(p.Val27Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,613,614 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 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: FRY NM_023037.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 9.32

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, FRY
• BP4: Computational evidence support a benign effect (MetaRNN=0.0094097555).
• BP6: Variant 13-32078842-G-A is Benign according to our data. Variant chr13-32078842-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 738354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 140 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRY	NM_023037.3	c.79G>A	p.Val27Ile	missense_variant	2/61	ENST00000542859.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRY	ENST00000542859.6	c.79G>A	p.Val27Ile	missense_variant	2/61	5	NM_023037.3	A1

Frequencies

GnomAD3 genomes AF: 0.000921 AC: 140 AN: 152034 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000425 AC: 106 AN: 249508 Hom.: 0 AF XY: 0.000414 AC XY: 56 AN XY: 135370

Gnomad AFR exome AF: 0.00291

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000530

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000213 AC: 312 AN: 1461462 Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 146 AN XY: 727068

Gnomad4 AFR exome AF: 0.00314

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00406

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.000547

GnomAD4 genome AF: 0.000927 AC: 141 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000887 AC XY: 66 AN XY: 74376

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000422 Hom.: 0

Bravo AF: 0.000880

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00130 AC: 5

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000463 AC: 56

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.072
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.0094	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.64	T
Polyphen		0.19	.;.;.;B;.
Vest4		0.39, 0.69
MVP		0.10
MPC		0.38
ClinPred		0.095	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.26

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

LitVar

Other links and lift over

dbSNP: rs35417728; hg19: chr13-32652979;