Variant 10-125988573-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145235.5(FANK1):c.214G>T(p.Val72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

FANK1
NM_145235.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.503

Variant links:

Genes affected

FANK1 (HGNC:23527): (fibronectin type III and ankyrin repeat domains 1) Involved in regulation of apoptotic process and regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

FANK1 links:

FANK1 (HGNC:):

FANK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03682691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANK1	NM_145235.5 linkuse as main transcript	c.214G>T	p.Val72Phe	missense_variant	3/11	ENST00000368693.6	NP_660278.3	Q8TC84-1
FANK1	NM_001350939.2 linkuse as main transcript	c.214G>T	p.Val72Phe	missense_variant	3/12		NP_001337868.1
FANK1	NM_001363549.2 linkuse as main transcript	c.196G>T	p.Val66Phe	missense_variant	3/11		NP_001350478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANK1	ENST00000368693.6 linkuse as main transcript	c.214G>T	p.Val72Phe	missense_variant	3/11	1	NM_145235.5	ENSP00000357682.1		Q8TC84-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251258

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000217

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000769

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000249

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.214G>T (p.V72F) alteration is located in exon 3 (coding exon 3) of the FANK1 gene. This alteration results from a G to T substitution at nucleotide position 214, causing the valine (V) at amino acid position 72 to be replaced by a phenylalanine (F). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0049

T;T;.;T;T;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.88

D;D;D;D;D;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.037

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

L;.;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.31

T;T;T;T;T;T

Sift4G

Benign

0.31

T;T;T;T;T;T

Polyphen

0.71

P;.;.;.;.;.

Vest4

0.48

MVP

0.28

MPC

0.37

ClinPred

0.027

GERP RS

2.2

Varity_R

0.093

gMVP

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over