7-100888850-A-T

Variant names:

• chr7-100888850-A-T
• rs199815193
• NM_001430944.2:c.650T>A

Variant summary

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

The NM_001430944.2(UFSP1):​c.650T>A​(p.Leu217*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: UFSP1 NM_001430944.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• 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]

SRRT (HGNC:24101): (serrate, RNA effector molecule) Enables mRNA cap binding complex binding activity and protein-macromolecule adaptor activity. Involved in primary miRNA processing. Located in nucleoplasm. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

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.650T>A	p.Leu217*	stop_gained	Exon 1 of 1	NP_001417873.1	Q6NVU6
	UFSP1	NM_001015072.4		c.422T>A	p.Leu141*	stop_gained	Exon 1 of 1	NP_001015072.2	A0AAR1ZLH9
	SRRT	NM_015908.6	MANE Select	c.*301A>T		downstream_gene	N/A	NP_056992.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFSP1	ENST00000672365.3	MANE Select	c.650T>A	p.Leu217*	stop_gained	Exon 1 of 1	ENSP00000499910.2	Q6NVU6
	UFSP1	ENST00000388761.4	TSL:6	c.422T>A	p.Leu141*	stop_gained	Exon 1 of 1	ENSP00000373413.2	A0AAR1ZLH9
	SRRT	ENST00000611405.5	TSL:1 MANE Select	c.*301A>T		downstream_gene	N/A	ENSP00000480421.1	Q9BXP5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455068 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722994

African (AFR) AF: 0.00 AC: 0 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25596

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.00 AC: 0 AN: 85622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107592

Other (OTH) AF: 0.00 AC: 0 AN: 60028

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	29
DANN	Uncertain	0.97
Eigen	Benign	0.096
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.32	N
PhyloP100		-0.96
Vest4		0.030
GERP RS		3.4
Mutation Taster		=153/47	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: rs199815193; hg19: chr7-100486471;