Genetic Variant NM_015323.5:c.958G>A (chr6-96537529-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_015323.5(UFL1):c.958G>A(p.Gly320Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000269 in 1,596,648 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000029 ( 2 hom. )

Consequence

UFL1
NM_015323.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

Publications

0 publications found

Variant links:

Genes affected

UFL1 (HGNC:23039): (UFM1 specific ligase 1) Enables UFM1 ligase activity and protein kinase binding activity. Involved in several processes, including cellular protein modification process; regulation of signal transduction; and reticulophagy. Acts upstream of or within several processes, including positive regulation of cell population proliferation; regulation of proteasomal ubiquitin-dependent protein catabolic process; and response to endoplasmic reticulum stress. Located in endoplasmic reticulum membrane; nucleus; and site of double-strand break. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

UFL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3115428).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015323.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFL1	NM_015323.5	MANE Select	c.958G>A	p.Gly320Arg	missense	Exon 9 of 19	NP_056138.1	O94874-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UFL1	ENST00000369278.5	TSL:1 MANE Select	c.958G>A	p.Gly320Arg	missense	Exon 9 of 19	ENSP00000358283.4	O94874-1
UFL1	ENST00000863356.1		c.955G>A	p.Gly319Arg	missense	Exon 9 of 19	ENSP00000533415.1
UFL1	ENST00000863355.1		c.958G>A	p.Gly320Arg	missense	Exon 9 of 19	ENSP00000533414.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000343

AC:

AN:

233046

AF XY:

0.0000396

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000291

AC:

AN:

1444854

Hom.:

Cov.:

AF XY:

0.0000473

AC XY:

AN XY:

718644

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31950

American (AMR)

AF:

0.00

AC:

AN:

40878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25254

East Asian (EAS)

AF:

0.00

AC:

AN:

39018

South Asian (SAS)

AF:

0.000503

AC:

AN:

83514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105906

Other (OTH)

AF:

0.00

AC:

AN:

59568

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151794

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41382

American (AMR)

AF:

0.00

AC:

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67858

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0098

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

6.0

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.17

Sift

Uncertain

0.015

Sift4G

Benign

0.22

Polyphen

0.27

Vest4

0.61

MutPred

0.54

Loss of helix (P = 0.0237)

MVP

0.38

MPC

0.60

ClinPred

0.60

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.39

gMVP

0.63

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over