7-100889157-G-A

Variant names:

• chr7-100889157-G-A
• rs201307521
• NM_001430944.2:c.343C>T

Variant summary

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

The NM_001430944.2(UFSP1):​c.343C>T​(p.Arg115Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,612,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UFSP1 NM_001430944.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 1 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=0.17864975).

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.343C>T	p.Arg115Trp	missense	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.115C>T	p.Arg39Trp	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.343C>T	p.Arg115Trp	missense	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.115C>T	p.Arg39Trp	missense	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152126 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 244908 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460478 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726492

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111740

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152244 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41546

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.79	T
PhyloP100		2.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.31
MVP		0.18
MPC		0.098
ClinPred		0.96	D
GERP RS		3.0
PromoterAI		-0.0014	Neutral
Varity_R		0.26
gMVP		0.34
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201307521; hg19: chr7-100486778;