Variant 10-125980166-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145235.5(FANK1):c.19A>T(p.Met7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FANK1
NM_145235.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.91

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11702618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANK1	NM_145235.5 linkuse as main transcript	c.19A>T	p.Met7Leu	missense_variant	2/11	ENST00000368693.6	NP_660278.3	Q8TC84-1
FANK1	NM_001350939.2 linkuse as main transcript	c.19A>T	p.Met7Leu	missense_variant	2/12		NP_001337868.1
FANK1	NM_001363549.2 linkuse as main transcript	c.1A>T	p.Met1?	initiator_codon_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.19A>T	p.Met7Leu	missense_variant	2/11	1	NM_145235.5	ENSP00000357682.1		Q8TC84-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453752

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722812

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 19, 2024

The c.19A>T (p.M7L) alteration is located in exon 2 (coding exon 2) of the FANK1 gene. This alteration results from a A to T substitution at nucleotide position 19, causing the methionine (M) at amino acid position 7 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

0.074

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.038

DANN

Benign

0.73

DEOGEN2

Benign

0.0022

T;T;.;T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.30

T;D;D;D;D;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.056

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

L;.;.;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.33

N;N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.24

T;T;T;T;T;T

Sift4G

Benign

0.32

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;.

Vest4

0.089

MutPred

0.11

Gain of catalytic residue at M7 (P = 0.0539);.;.;.;.;.;

MVP

0.25

MPC

0.13

ClinPred

0.060

GERP RS

-6.3

Varity_R

0.070

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over