Variant 14-45159080-TTATA-TTA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_020937.4(FANCM):c.1397-3_1397-2del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,415,016 control chromosomes in the GnomAD database, including 8,448 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.091 ( 764 hom., cov: 30)

Exomes 𝑓: 0.11 ( 7684 hom. )

Consequence

FANCM
NM_020937.4 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 0.918

Variant links:

Genes affected

FANCM (HGNC:23168): (FA complementation group M) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group M. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

FANCM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 14-45159080-TTA-T is Benign according to our data. Variant chr14-45159080-TTA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261381.We mark this variant Likely_benign, oryginal submissions are: {Benign=5, Uncertain_significance=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FANCM	NM_020937.4 linkuse as main transcript	c.1397-3_1397-2del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000267430.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FANCM	ENST00000267430.10 linkuse as main transcript	c.1397-3_1397-2del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020937.4	P1	Q8IYD8-1

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13782

AN:

151270

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.177

AC:

23609

AN:

133184

Hom.:

1461

AF XY:

0.183

AC XY:

13210

AN XY:

72324

show subpopulations

Gnomad AFR exome

AF:

0.0653

Gnomad AMR exome

AF:

0.210

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.170

GnomAD4 exome

AF:

0.112

AC:

141719

AN:

1263634

Hom.:

7684

AF XY:

0.115

AC XY:

72393

AN XY:

629880

show subpopulations

Gnomad4 AFR exome

AF:

0.0401

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.131

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.0911

AC:

13789

AN:

151382

Hom.:

764

Cov.:

AF XY:

0.0928

AC XY:

6862

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.0383

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.118

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.116

Alfa

AF:

0.0762

Hom.:

128

Bravo

AF:

0.0893

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 08, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Premature ovarian failure 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Spermatogenic failure 28

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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