chr14-93215267-C-T

Variant names:

• chr14-93215267-C-T
• rs371330936
• NM_175748.4:c.587C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_175748.4(UBR7):​c.587C>T​(p.Ala196Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,578,772 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: UBR7 NM_175748.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

UBR7 (HGNC:20344): (ubiquitin protein ligase E3 component n-recognin 7) This gene encodes a UBR box-containing protein that belongs to the E3 ubiquitin ligase family. The protein also contains a plant homeodomain (PHD) in the C-terminus. In mammals, the encoded protein recognizes N-degrons, the destabilizing N-terminal residues of short-lived proteins, which results in ubiquitinylation, and proteolysis via the proteasome. [provided by RefSeq, Jul 2016]

UBR7 Gene-Disease associations (from GenCC):

• Li-Campeau syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000259066 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000046 (7/152268) while in subpopulation AFR AF = 0.000168 (7/41570). AF 95% confidence interval is 0.0000787. There are 1 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175748.4. 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
	UBR7	NM_175748.4	MANE Select	c.587C>T	p.Ala196Val	missense	Exon 6 of 11	NP_786924.2	Q8N806
	UBR7	NR_038150.2		n.489C>T		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBR7	ENST00000013070.11	TSL:1 MANE Select	c.587C>T	p.Ala196Val	missense	Exon 6 of 11	ENSP00000013070.6	Q8N806
	UBR7	ENST00000966805.1		c.620C>T	p.Ala207Val	missense	Exon 6 of 11	ENSP00000636864.1
	UBR7	ENST00000940497.1		c.587C>T	p.Ala196Val	missense	Exon 6 of 11	ENSP00000610556.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152150 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000103 AC: 2 AN: 194532 AF XY: 0.00000969

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: 0.0000121

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000329 AC: 47 AN: 1426504 Hom.: 0 Cov.: 31 AF XY: 0.0000439 AC XY: 31 AN XY: 705940

African (AFR) AF: 0.000513 AC: 17 AN: 33128

American (AMR) AF: 0.00 AC: 0 AN: 38744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25378

East Asian (EAS) AF: 0.00 AC: 0 AN: 38804

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51156

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093086

Other (OTH) AF: 0.000474 AC: 28 AN: 59104

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152268 Hom.: 1 Cov.: 33 AF XY: 0.0000672 AC XY: 5 AN XY: 74446

African (AFR) AF: 0.000168 AC: 7 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000167 AC: 2

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.0
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.52	N
REVEL	Uncertain	0.41
Sift	Benign	0.15	T
Sift4G	Benign	0.34	T
Polyphen		0.21	B
Vest4		0.59
MutPred		0.52		Gain of helix (P = 0.1736)
MVP		0.86
MPC		0.93
ClinPred		0.73	D
GERP RS		4.6
Varity_R		0.090
gMVP		0.69
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs371330936; hg19: chr14-93681613;