chr14-45137084-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020937.4(FANCM):c.524C>T(p.Ser175Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,611,518 control chromosomes in the GnomAD database, including 10,272 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 3753 hom., cov: 33)

Exomes 𝑓: 0.072 ( 6519 hom. )

Consequence

FANCM
NM_020937.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0520

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025475323).

BP6

Variant 14-45137084-C-T is Benign according to our data. Variant chr14-45137084-C-T is described in ClinVar as [Benign]. Clinvar id is 261389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCM	NM_020937.4 link	c.524C>T	p.Ser175Phe	missense_variant	Exon 2 of 23	ENST00000267430.10	NP_065988.1	Q8IYD8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCM	ENST00000267430.10 link	c.524C>T	p.Ser175Phe	missense_variant	Exon 2 of 23	1	NM_020937.4	ENSP00000267430.5		Q8IYD8-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24713

AN:

152020

Hom.:

3720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0915

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0575

Gnomad OTH

AF:

0.148

GnomAD3 exomes

AF:

0.101

AC:

25456

AN:

251258

Hom.:

2244

AF XY:

0.0964

AC XY:

13096

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.408

Gnomad AMR exome

AF:

0.0835

Gnomad ASJ exome

AF:

0.0694

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0878

Gnomad NFE exome

AF:

0.0581

Gnomad OTH exome

AF:

0.0806

GnomAD4 exome

AF:

0.0721

AC:

105260

AN:

1459380

Hom.:

6519

Cov.:

AF XY:

0.0727

AC XY:

52796

AN XY:

726182

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.0853

Gnomad4 ASJ exome

AF:

0.0700

Gnomad4 EAS exome

AF:

0.136

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0912

Gnomad4 NFE exome

AF:

0.0529

Gnomad4 OTH exome

AF:

0.0899

GnomAD4 genome

AF:

0.163

AC:

24798

AN:

152138

Hom.:

3753

Cov.:

AF XY:

0.161

AC XY:

12006

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.403

Gnomad4 AMR

AF:

0.0911

Gnomad4 ASJ

AF:

0.0643

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0818

Gnomad4 NFE

AF:

0.0575

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.0775

Hom.:

2185

Bravo

AF:

0.173

TwinsUK

AF:

0.0499

AC:

185

ALSPAC

AF:

0.0509

AC:

196

ESP6500AA

AF:

0.395

AC:

1741

ESP6500EA

AF:

0.0552

AC:

475

ExAC

AF:

0.109

AC:

13269

Asia WGS

AF:

0.136

AC:

476

AN:

3478

EpiCase

AF:

0.0543

EpiControl

AF:

0.0606

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Dec 05, 2016

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Premature ovarian failure 15

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.087

.;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.013

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

M;M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

1.7

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.055

T;T;T

Sift4G

Uncertain

0.055

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.052

MPC

0.094

ClinPred

0.0041

GERP RS

4.2

Varity_R

0.076

gMVP

0.15

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

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