rs1474358439

Variant names:

• chr6-96526340-G-T
• rs1474358439
• NM_015323.5:c.370G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-96526340-G-T
• chr6-96526340-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015323.5(UFL1):​c.370G>T​(p.Ala124Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,848 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: UFL1 NM_015323.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.49
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28915808).

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.370G>T	p.Ala124Ser	missense	Exon 5 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.370G>T	p.Ala124Ser	missense	Exon 5 of 19	ENSP00000358283.4	O94874-1
	UFL1	ENST00000863356.1		c.367G>T	p.Ala123Ser	missense	Exon 5 of 19	ENSP00000533415.1
	UFL1	ENST00000863355.1		c.370G>T	p.Ala124Ser	missense	Exon 5 of 19	ENSP00000533414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250872 AF XY: 0.0000147

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: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460848 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726730

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 86058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111570

Other (OTH) AF: 0.0000166 AC: 1 AN: 60348

GnomAD4 genome Cov.: 32

Alfa AF: 0.000223 Hom.: 0

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	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.5
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.18
Sift	Benign	0.065	T
Sift4G	Uncertain	0.044	D
Polyphen		0.096	B
Vest4		0.33
MutPred		0.60		Gain of phosphorylation at A124 (P = 0.0195)
MVP		0.37
MPC		0.31
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.38
gMVP		0.63
Mutation Taster		=77/23	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: rs1474358439; hg19: chr6-96974216;