rs147577102

Variant names:

• chr6-96528607-C-T
• rs147577102
• NM_015323.5:c.571C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015323.5(UFL1):​c.571C>T​(p.Arg191Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,613,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (0 hom.)
• Consequence: UFL1 NM_015323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1898515).

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.571C>T	p.Arg191Cys	missense	Exon 6 of 19	NP_056138.1	O94874-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFL1	ENST00000369278.5	TSL:1 MANE Select	c.571C>T	p.Arg191Cys	missense	Exon 6 of 19	ENSP00000358283.4	O94874-1
	UFL1	ENST00000863356.1		c.568C>T	p.Arg190Cys	missense	Exon 6 of 19	ENSP00000533415.1
	UFL1	ENST00000863355.1		c.571C>T	p.Arg191Cys	missense	Exon 6 of 19	ENSP00000533414.1

Frequencies

GnomAD3 genomes AF: 0.000493 AC: 75 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000617 AC: 155 AN: 251114 AF XY: 0.000744

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000924

Gnomad NFE exome AF: 0.00106

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000701 AC: 1024 AN: 1461380 Hom.: 0 Cov.: 30 AF XY: 0.000726 AC XY: 528 AN XY: 726992

African (AFR) AF: 0.000120 AC: 4 AN: 33462

American (AMR) AF: 0.0000448 AC: 2 AN: 44670

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86222

European-Finnish (FIN) AF: 0.000862 AC: 46 AN: 53390

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5764

European-Non Finnish (NFE) AF: 0.000825 AC: 917 AN: 1111706

Other (OTH) AF: 0.000364 AC: 22 AN: 60374

GnomAD4 genome AF: 0.000493 AC: 75 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.000525 AC XY: 39 AN XY: 74310

African (AFR) AF: 0.0000966 AC: 4 AN: 41414

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000761 Hom.: 0

Bravo AF: 0.000404

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000725 AC: 88

EpiCase AF: 0.000765

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.43
Sift	Benign	0.031	D
Sift4G	Benign	0.096	T
Polyphen		0.65	P
Vest4		0.54
MVP		0.39
MPC		0.29
ClinPred		0.15	T
GERP RS		5.4
Varity_R		0.46
gMVP		0.93
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs147577102; hg19: chr6-96976483; COSMIC: COSV104679472;