Variant 16-23557970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019116.3(UBFD1):c.46G>A(p.Asp16Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000287 in 1,364,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

UBFD1
NM_019116.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

UBFD1 (HGNC:30565): (ubiquitin family domain containing 1) Enables RNA binding activity and cadherin binding activity. [provided by Alliance of Genome Resources, Apr 2022]

UBFD1 links:

UBFD1 (HGNC:):

UBFD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08971843).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBFD1	NM_019116.3 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	2/7	ENST00000395878.8	NP_061989.2	O14562

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBFD1	ENST00000395878.8 linkuse as main transcript	c.46G>A	p.Asp16Asn	missense_variant	2/7	2	NM_019116.3	ENSP00000379217.3		O14562

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000117

AC:

AN:

77024

Hom.:

AF XY:

0.0000928

AC XY:

AN XY:

43110

show subpopulations

Gnomad AFR exome

AF:

0.000425

Gnomad AMR exome

AF:

0.000136

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:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000312

AC:

378

AN:

1212364

Hom.:

Cov.:

AF XY:

0.000342

AC XY:

201

AN XY:

587680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000636

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000371

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000708

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000316

AC:

ESP6500EA

AF:

0.000281

AC:

ExAC

AF:

0.0000894

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

Dec 03, 2024

The c.46G>A (p.D16N) alteration is located in exon 2 (coding exon 2) of the UBFD1 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the aspartic acid (D) at amino acid position 16 to be replaced by an asparagine (N). 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

0.18

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.60

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.090

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.88

N;N;N

REVEL

Benign

0.078

Sift

Uncertain

0.011

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.024

B;.;.

Vest4

0.30

MVP

0.38

MPC

0.72

ClinPred

0.12

GERP RS

3.6

Varity_R

0.22

gMVP

0.24

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