Variant chr10-125980324-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145235.5(FANK1):c.177T>C(p.Tyr59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,613,958 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 16 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 10 hom. )

Consequence

FANK1
NM_145235.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.689

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 10-125980324-T-C is Benign according to our data. Variant chr10-125980324-T-C is described in ClinVar as [Benign]. Clinvar id is 780916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00656 (999/152316) while in subpopulation AFR AF= 0.0226 (940/41562). AF 95% confidence interval is 0.0214. There are 16 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FANK1	NM_145235.5 linkuse as main transcript	c.177T>C	p.Tyr59=	synonymous_variant	2/11	ENST00000368693.6
FANK1	NM_001350939.2 linkuse as main transcript	c.177T>C	p.Tyr59=	synonymous_variant	2/12
FANK1	NM_001363549.2 linkuse as main transcript	c.159T>C	p.Tyr53=	synonymous_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANK1	ENST00000368693.6 linkuse as main transcript	c.177T>C	p.Tyr59=	synonymous_variant	2/11	1	NM_145235.5	P1	Q8TC84-1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

993

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00180

AC:

451

AN:

250972

Hom.:

AF XY:

0.00129

AC XY:

175

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000764

AC:

1117

AN:

1461642

Hom.:

Cov.:

AF XY:

0.000656

AC XY:

477

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0222

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00656

AC:

999

AN:

152316

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

479

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.00761

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.87

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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