7-100889216-T-A

Variant names:

• chr7-100889216-T-A
• rs746962787
• NM_001430944.2:c.284A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001430944.2(UFSP1):​c.284A>T​(p.Glu95Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,440,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E95K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: UFSP1 NM_001430944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

UFSP1 (HGNC:33821): (UFM1 specific peptidase 1 (inactive)) This gene encodes a protein that is similar to other Ufm1-specific proteases. Studies in mouse determined that Ufsp1 releases Ufm1 (ubiquitin-fold modifier 1) from its bound conjugated complexes which also makes it into an active form. Because the human UFSP1 protein is shorter on the N-terminus and lacks a conserved Cys active site, it is predicted to be non-functional.[provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.937

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001430944.2. 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
	UFSP1	NM_001430944.2	MANE Select	c.284A>T	p.Glu95Val	missense	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.56A>T	p.Glu19Val	missense	Exon 1 of 1	NP_001015072.2	A0AAR1ZLH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFSP1	ENST00000672365.3	MANE Select	c.284A>T	p.Glu95Val	missense	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.56A>T	p.Glu19Val	missense	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.000115 AC: 25 AN: 216660 AF XY: 0.000142

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000774

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: 0.0000174 AC: 25 AN: 1440924 Hom.: 0 Cov.: 33 AF XY: 0.0000196 AC XY: 14 AN XY: 715292

African (AFR) AF: 0.00 AC: 0 AN: 33148

American (AMR) AF: 0.000555 AC: 24 AN: 43230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24982

East Asian (EAS) AF: 0.00 AC: 0 AN: 39498

South Asian (SAS) AF: 0.00 AC: 0 AN: 84220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102940

Other (OTH) AF: 0.0000169 AC: 1 AN: 59344

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000845 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.014	T
PhyloP100		2.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.87		Gain of stability (P = 0.1273)
MVP		0.61
MPC		0.42
ClinPred		0.90	D
GERP RS		4.4
PromoterAI		-0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.98
gMVP		0.79
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746962787; hg19: chr7-100486837;