7-100889178-C-T

Variant names:

• chr7-100889178-C-T
• rs751881061
• NM_001430944.2:c.322G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001430944.2(UFSP1):​c.322G>A​(p.Gly108Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,611,562 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 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: UFSP1 NM_001430944.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.671
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27260095).

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.322G>A	p.Gly108Arg	missense	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.94G>A	p.Gly32Arg	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.322G>A	p.Gly108Arg	missense	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.94G>A	p.Gly32Arg	missense	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152170 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000826 AC: 20 AN: 242064 AF XY: 0.0000833

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: 0.0000943

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000114 AC: 166 AN: 1459392 Hom.: 0 Cov.: 33 AF XY: 0.000102 AC XY: 74 AN XY: 725902

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.0000383 AC: 2 AN: 52188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.000139 AC: 154 AN: 1111348

Other (OTH) AF: 0.000166 AC: 10 AN: 60302

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152170 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74324

African (AFR) AF: 0.0000241 AC: 1 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000433 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000413 AC: 5

EpiCase AF: 0.000273

EpiControl AF: 0.000119

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	0.69
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.67
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.15
Sift	Benign	0.074	T
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.67		Loss of catalytic residue at C35 (P = 0.0649)
MVP		0.32
MPC		0.42
ClinPred		0.92	D
GERP RS		4.4
PromoterAI		0.014	Neutral
Varity_R		0.51
gMVP		0.56
Mutation Taster		=82/18	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: rs751881061; hg19: chr7-100486799;