Variant 10-125980290-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145235.5(FANK1):c.143C>T(p.Ser48Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,461,868 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FANK1
NM_145235.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38600475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANK1	NM_145235.5 linkuse as main transcript	c.143C>T	p.Ser48Leu	missense_variant	2/11	ENST00000368693.6	NP_660278.3	Q8TC84-1
FANK1	NM_001350939.2 linkuse as main transcript	c.143C>T	p.Ser48Leu	missense_variant	2/12		NP_001337868.1
FANK1	NM_001363549.2 linkuse as main transcript	c.125C>T	p.Ser42Leu	missense_variant	2/11		NP_001350478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANK1	ENST00000368693.6 linkuse as main transcript	c.143C>T	p.Ser48Leu	missense_variant	2/11	1	NM_145235.5	ENSP00000357682.1		Q8TC84-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251378

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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 11, 2023

The c.143C>T (p.S48L) alteration is located in exon 2 (coding exon 2) of the FANK1 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the serine (S) at amino acid position 48 to be replaced by a leucine (L). 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

Benign

0.23

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0045

T;T;.;T;T;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.39

T;T;T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.8

L;.;.;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.82

N;N;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.31

T;T;T;T;T;T

Sift4G

Benign

0.081

T;T;T;D;T;D

Polyphen

0.98

D;.;.;.;.;.

Vest4

0.73

MutPred

0.58

Loss of loop (P = 9e-04);.;.;.;.;.;

MVP

0.48

MPC

0.42

ClinPred

0.46

GERP RS

5.0

Varity_R

0.13

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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