2-31868409-C-G

Variant names:

• chr2-31868409-C-G
• NM_001301833.4:c.846G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001301833.4(MEMO1):​c.846G>C​(p.Trp282Cys) 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 (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MEMO1 NM_001301833.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89

Genes affected

MEMO1 (HGNC:14014): (mediator of cell motility 1) Involved in regulation of microtubule-based process. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DPY30 (HGNC:24590): (dpy-30 histone methyltransferase complex regulatory subunit) This gene encodes an integral core subunit of the SET1/MLL family of H3K4 methyltransferases. The encoded protein directly controls cell cycle regulators and plays an important role in the proliferation and differentiation of human hematopoietic progenitor cells. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4170777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEMO1	NM_001301833.4	c.846G>C	p.Trp282Cys	missense_variant	Exon 10 of 10	ENST00000404530.6	NP_001288762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEMO1	ENST00000404530.6	c.846G>C	p.Trp282Cys	missense_variant	Exon 10 of 10	2	NM_001301833.4	ENSP00000385557.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.846G>C (p.W282C) alteration is located in exon 9 (coding exon 9) of the MEMO1 gene. This alteration results from a G to C substitution at nucleotide position 846, causing the tryptophan (W) at amino acid position 282 to be replaced by a cysteine (C). 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	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.069	T;.;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.99	.;D;D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L;.;L;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.20
Sift	Benign	0.17	T;T;T;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.96	D;.;D;P
Vest4		0.61
MutPred		0.32		Gain of disorder (P = 0.043);.;Gain of disorder (P = 0.043);.;
MVP		0.082
MPC		1.7
ClinPred		0.85	D
GERP RS		5.2
Varity_R		0.39
gMVP		0.90

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: chr2-32093478;