chrX-155046553-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023934.4(FUNDC2):​c.329C>T​(p.Thr110Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Consequence

FUNDC2
NM_023934.4 missense

Scores

3
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.48
Variant links:
Genes affected
FUNDC2 (HGNC:24925): (FUN14 domain containing 2) Predicted to be involved in autophagy of mitochondrion. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FUNDC2NM_023934.4 linkc.329C>T p.Thr110Ile missense_variant Exon 3 of 5 ENST00000369498.8 NP_076423.2 Q9BWH2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FUNDC2ENST00000369498.8 linkc.329C>T p.Thr110Ile missense_variant Exon 3 of 5 1 NM_023934.4 ENSP00000358510.3 Q9BWH2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000545
AC:
1
AN:
183471
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67909
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
22
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.329C>T (p.T110I) alteration is located in exon 3 (coding exon 3) of the FUNDC2 gene. This alteration results from a C to T substitution at nucleotide position 329, causing the threonine (T) at amino acid position 110 to be replaced by an isoleucine (I). 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
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0080
T
MetaRNN
Uncertain
0.70
D
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.21
Sift
Benign
0.24
T
Sift4G
Benign
0.16
T
Polyphen
0.98
D
Vest4
0.61
MutPred
0.49
Gain of ubiquitination at K106 (P = 0.1278);
MVP
0.67
MPC
0.90
ClinPred
0.99
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.36
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.25
Position offset: 31

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.

Other links and lift over

dbSNP: rs782087072; hg19: chrX-154274828; API