Variant X-44542816-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_173794.4(FUNDC1):c.17C>A(p.Pro6His) variant causes a missense change. The variant allele was found at a frequency of 0.00000942 in 1,167,851 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000076 ( 0 hom. 4 hem. )

Consequence

FUNDC1
NM_173794.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2864499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FUNDC1	NM_173794.4 linkuse as main transcript	c.17C>A	p.Pro6His	missense_variant	1/5	ENST00000378045.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FUNDC1	ENST00000378045.5 linkuse as main transcript	c.17C>A	p.Pro6His	missense_variant	1/5	1	NM_173794.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34200

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

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:

0.00

Gnomad OTH

AF:

0.00133

GnomAD3 exomes

AF:

0.00000879

AC:

AN:

113812

Hom.:

AF XY:

0.0000282

AC XY:

AN XY:

35506

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:

0.00

Gnomad OTH exome

AF:

0.000321

GnomAD4 exome

AF:

0.00000758

AC:

AN:

1055823

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

343527

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000201

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000122

Gnomad4 OTH exome

AF:

0.0000450

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000944

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00133

Bravo

AF:

0.0000264

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

Feb 05, 2024

The c.17C>A (p.P6H) alteration is located in exon 1 (coding exon 1) of the FUNDC1 gene. This alteration results from a C to A substitution at nucleotide position 17, causing the proline (P) at amino acid position 6 to be replaced by a histidine (H). 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

0.079

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.013

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.62

M_CAP

Benign

0.012

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-0.69

REVEL

Benign

0.10

Sift

Uncertain

0.011

Sift4G

Uncertain

0.056

Polyphen

0.98

Vest4

0.39

MutPred

0.12

Loss of glycosylation at P6 (P = 0.0359);

MVP

0.66

MPC

0.16

ClinPred

0.31

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.25

gMVP

0.27

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