6-96537381-T-G

Variant names:

• chr6-96537381-T-G
• rs199627983
• NM_015323.5:c.810T>G

Variant summary

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

The NM_015323.5(UFL1):​c.810T>G​(p.Asp270Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000418 in 1,556,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: UFL1 NM_015323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83
• Publications: 0 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=0.17676178).

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.810T>G	p.Asp270Glu	missense	Exon 9 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.810T>G	p.Asp270Glu	missense	Exon 9 of 19	ENSP00000358283.4	O94874-1
	UFL1	ENST00000863356.1		c.807T>G	p.Asp269Glu	missense	Exon 9 of 19	ENSP00000533415.1
	UFL1	ENST00000863355.1		c.810T>G	p.Asp270Glu	missense	Exon 9 of 19	ENSP00000533414.1

Frequencies

GnomAD3 genomes AF: 0.0000593 AC: 9 AN: 151866 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

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: 0.0000737

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000806 AC: 16 AN: 198490 AF XY: 0.0000553

Gnomad AFR exome AF: 0.0000736

Gnomad AMR exome AF: 0.0000908

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000947

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000406 AC: 57 AN: 1404826 Hom.: 0 Cov.: 30 AF XY: 0.0000458 AC XY: 32 AN XY: 698028

African (AFR) AF: 0.0000340 AC: 1 AN: 29452

American (AMR) AF: 0.0000642 AC: 2 AN: 31154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23104

East Asian (EAS) AF: 0.00 AC: 0 AN: 37264

South Asian (SAS) AF: 0.000116 AC: 9 AN: 77798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52024

Middle Eastern (MID) AF: 0.00201 AC: 11 AN: 5468

European-Non Finnish (NFE) AF: 0.0000293 AC: 32 AN: 1090924

Other (OTH) AF: 0.0000347 AC: 2 AN: 57638

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 151984 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74288

African (AFR) AF: 0.0000241 AC: 1 AN: 41526

American (AMR) AF: 0.000132 AC: 2 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67880

Other (OTH) AF: 0.00 AC: 0 AN: 2102

Alfa AF: 0.000110 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000824 AC: 10

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	0.28
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.8
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.17
Sift	Benign	0.062	T
Sift4G	Benign	0.070	T
Polyphen		0.83	P
Vest4		0.42
MutPred		0.70		Loss of sheet (P = 0.1158)
MVP		0.17
MPC		0.54
ClinPred		0.18	T
GERP RS		3.4
Varity_R		0.30
gMVP		0.58
Mutation Taster		=83/17	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: rs199627983; hg19: chr6-96985257;