chr1-161156979-C-T

Variant names:

• chr1-161156979-C-T
• rs142789001
• NM_016406.4:c.153C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_016406.4(UFC1):​c.153C>T​(p.Asn51Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,614,228 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: UFC1 NM_016406.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0350
• Publications: 1 publications found

Genes affected

UFC1 (HGNC:26941): (ubiquitin-fold modifier conjugating enzyme 1) UFC1 is an E2-like conjugating enzyme for ubiquitin-fold modifier-1 (UFM1; MIM 610553) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Mar 2008]

UFC1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with spasticity and poor growth

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000224985 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-161156979-C-T is Benign according to our data. Variant chr1-161156979-C-T is described in ClinVar as Benign. ClinVar VariationId is 3043955.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.035 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016406.4. 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
	UFC1	NM_016406.4	MANE Select	c.153C>T	p.Asn51Asn	synonymous	Exon 2 of 6	NP_057490.2	Q9Y3C8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UFC1	ENST00000368003.6	TSL:1 MANE Select	c.153C>T	p.Asn51Asn	synonymous	Exon 2 of 6	ENSP00000356982.5	Q9Y3C8
	UFC1	ENST00000482672.1	TSL:1	n.116C>T		non_coding_transcript_exon	Exon 2 of 2
	UFC1	ENST00000913804.1		c.153C>T	p.Asn51Asn	synonymous	Exon 3 of 7	ENSP00000583863.1

Frequencies

GnomAD3 genomes AF: 0.00416 AC: 633 AN: 152240 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000982 AC: 247 AN: 251476 AF XY: 0.000736

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000412 AC: 602 AN: 1461870 Hom.: 6 Cov.: 31 AF XY: 0.000344 AC XY: 250 AN XY: 727244

African (AFR) AF: 0.0135 AC: 452 AN: 33480

American (AMR) AF: 0.00103 AC: 46 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111996

Other (OTH) AF: 0.00134 AC: 81 AN: 60396

GnomAD4 genome AF: 0.00417 AC: 635 AN: 152358 Hom.: 5 Cov.: 33 AF XY: 0.00430 AC XY: 320 AN XY: 74504

African (AFR) AF: 0.0139 AC: 579 AN: 41578

American (AMR) AF: 0.00314 AC: 48 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00466

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	UFC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	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: rs142789001; hg19: chr1-161126769; COSMIC: COSV99237223; COSMIC: COSV99237223;