1-20501048-T-C

Position:

• chr1-20501048-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000264198.5(MUL1):​c.701A>G​(p.Glu234Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E234A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MUL1 ENST00000264198.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.80

Genes affected

MUL1 (HGNC:25762): (mitochondrial E3 ubiquitin protein ligase 1) Enables several functions, including p53 binding activity; ubiquitin protein ligase binding activity; and ubiquitin-like protein transferase activity. Involved in several processes, including negative regulation of defense response; positive regulation of cellular protein metabolic process; and regulation of mitochondrion organization. Located in several cellular components, including mitochondrion; neuronal cell body; and peroxisome. Is integral component of mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16758123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MUL1	NM_024544.3	c.701A>G	p.Glu234Gly	missense_variant	4/4	ENST00000264198.5	NP_078820.2
MUL1	XM_011542137.3	c.584A>G	p.Glu195Gly	missense_variant	4/4		XP_011540439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MUL1	ENST00000264198.5	c.701A>G	p.Glu234Gly	missense_variant	4/4	1	NM_024544.3	ENSP00000264198	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 01, 2023

The c.701A>G (p.E234G) alteration is located in exon 4 (coding exon 4) of the MUL1 gene. This alteration results from a A to G substitution at nucleotide position 701, causing the glutamic acid (E) at amino acid position 234 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.051
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.090
Sift	Benign	0.063	T
Sift4G	Benign	0.17	T
Polyphen		0.071	B
Vest4		0.059
MutPred		0.33		Gain of MoRF binding (P = 0.0503);
MVP		0.41
MPC		0.43
ClinPred		0.78	D
GERP RS		6.2
Varity_R		0.24
gMVP		0.57

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-20827541;