Variant X-44542000-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_173794.4(FUNDC1):c.130A>G(p.Met44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,205,116 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 39 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00012 ( 0 hom. 34 hem. )

Consequence

FUNDC1
NM_173794.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

FUNDC1 (HGNC:28746): (FUN14 domain containing 1) This gene encodes a protein with a FUN14 superfamily domain. The function of the encoded protein is not known. [provided by RefSeq, Sep 2011]

FUNDC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048868746).

BS2

High Hemizygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUNDC1	NM_173794.4 linkuse as main transcript	c.130A>G	p.Met44Val	missense_variant	2/5	ENST00000378045.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUNDC1	ENST00000378045.5 linkuse as main transcript	c.130A>G	p.Met44Val	missense_variant	2/5	1	NM_173794.4	P1
FUNDC1	ENST00000483115.1 linkuse as main transcript	n.305A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.000170

AC:

AN:

111451

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33633

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000963

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

176736

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

61484

show subpopulations

Gnomad AFR exome

AF:

0.0000783

Gnomad AMR exome

AF:

0.0000374

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000395

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000118

AC:

129

AN:

1093665

Hom.:

Cov.:

AF XY:

0.0000947

AC XY:

AN XY:

359177

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000149

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.000170

AC:

AN:

111451

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

33633

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000963

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000159

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000595

AC:

ExAC

AF:

0.000173

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

Mar 14, 2023

The c.130A>G (p.M44V) alteration is located in exon 2 (coding exon 2) of the FUNDC1 gene. This alteration results from a A to G substitution at nucleotide position 130, causing the methionine (M) at amino acid position 44 to be replaced by a valine (V). 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

0.061

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.51

Cadd

Benign

Dann

Benign

0.63

DEOGEN2

Benign

0.010

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.69

M_CAP

Benign

0.018

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.95

MutationTaster

Benign

0.86

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.39

REVEL

Benign

0.091

Sift

Benign

1.0

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.095

MVP

0.61

MPC

0.064

ClinPred

0.038

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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