rs12666989

Variant names:

• chr7-100889133-G-C
• rs12666989
• NM_001430944.2:c.367C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-100889133-G-C
• chr7-100889133-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001430944.2(UFSP1):​c.367C>G​(p.Leu123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,612,576 control chromosomes in the GnomAD database, including 24,507 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.13 (1707 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22800 hom.)
• Consequence: UFSP1 NM_001430944.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.613
• Publications: 50 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011535585).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

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.367C>G	p.Leu123Val	missense	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.139C>G	p.Leu47Val	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.367C>G	p.Leu123Val	missense	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.139C>G	p.Leu47Val	missense	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20303 AN: 152012 Hom.: 1712 Cov.: 33

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.140

GnomAD2 exomes AF: 0.154 AC: 37966 AN: 247086 AF XY: 0.155

Gnomad AFR exome AF: 0.0484

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.0398

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.172 AC: 250663 AN: 1460446 Hom.: 22800 Cov.: 35 AF XY: 0.171 AC XY: 124011 AN XY: 726450

African (AFR) AF: 0.0490 AC: 1640 AN: 33468

American (AMR) AF: 0.126 AC: 5631 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 5615 AN: 26078

East Asian (EAS) AF: 0.0271 AC: 1077 AN: 39690

South Asian (SAS) AF: 0.127 AC: 10964 AN: 86180

European-Finnish (FIN) AF: 0.213 AC: 11209 AN: 52710

Middle Eastern (MID) AF: 0.206 AC: 1179 AN: 5736

European-Non Finnish (NFE) AF: 0.183 AC: 203698 AN: 1111534

Other (OTH) AF: 0.160 AC: 9650 AN: 60368

GnomAD4 genome AF: 0.133 AC: 20299 AN: 152130 Hom.: 1707 Cov.: 33 AF XY: 0.132 AC XY: 9797 AN XY: 74354

African (AFR) AF: 0.0516 AC: 2144 AN: 41524

American (AMR) AF: 0.106 AC: 1623 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3472

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5178

South Asian (SAS) AF: 0.112 AC: 541 AN: 4816

European-Finnish (FIN) AF: 0.209 AC: 2210 AN: 10584

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12364 AN: 67948

Other (OTH) AF: 0.139 AC: 294 AN: 2114

Alfa AF: 0.178 Hom.: 897

Bravo AF: 0.123

TwinsUK AF: 0.176 AC: 651

ALSPAC AF: 0.175 AC: 674

ESP6500AA AF: 0.0563 AC: 248

ESP6500EA AF: 0.178 AC: 1532

ExAC AF: 0.153 AC: 18572

Asia WGS AF: 0.0790 AC: 275 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.7
DANN	Benign	0.43
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.023
Sift	Benign	0.68	T
Sift4G	Benign	0.30	T
Polyphen		0.77	P
Vest4		0.065
MPC		0.068
ClinPred		0.028	T
GERP RS		2.5
PromoterAI		0.035	Neutral
Varity_R		0.076
gMVP		0.19
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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; COSMIC: COSV53817007; COSMIC: COSV53817007;