chr7-100889133-G-T

Variant names:

• chr7-100889133-G-T
• rs12666989
• NM_001015072.4:c.139C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001015072.4(UFSP1):​c.139C>A​(p.Leu47Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UFSP1 NM_001015072.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19601405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UFSP1	NM_001015072.4	c.139C>A	p.Leu47Met	missense_variant	Exon 1 of 1	ENST00000388761.4	NP_001015072.2
UFSP1	NM_001430944.2	c.367C>A	p.Leu123Met	missense_variant	Exon 1 of 1		NP_001417873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UFSP1	ENST00000388761.4	c.139C>A	p.Leu47Met	missense_variant	Exon 1 of 1	6	NM_001015072.4	ENSP00000373413.2
UFSP1	ENST00000672365.3	c.367C>A	p.Leu123Met	missense_variant	Exon 1 of 1			ENSP00000499910.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460794 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726636

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
PhyloP100		0.61
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.047
Sift	Benign	0.14	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.27
MutPred		0.44		Gain of disorder (P = 0.114);
MVP		0.14
MPC		0.16
ClinPred		0.89	D
GERP RS		2.5
PromoterAI		-0.0084	Neutral
Varity_R		0.15
gMVP		0.27
Mutation Taster		=88/12	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: rs12666989; hg19: chr7-100486754;