Variant 2-31932104-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001301833.4(MEMO1):c.175G>T(p.Ala59Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,376 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MEMO1
NM_001301833.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

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]

MEMO1 links:

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]

DPY30 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEMO1	NM_001301833.4 linkuse as main transcript	c.175G>T	p.Ala59Ser	missense_variant	4/10	ENST00000404530.6	NP_001288762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEMO1	ENST00000404530.6 linkuse as main transcript	c.175G>T	p.Ala59Ser	missense_variant	4/10	2	NM_001301833.4	ENSP00000385557	P1	Q9Y316-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461376

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.175G>T (p.A59S) alteration is located in exon 3 (coding exon 3) of the MEMO1 gene. This alteration results from a G to T substitution at nucleotide position 175, causing the alanine (A) at amino acid position 59 to be replaced by a serine (S). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.;T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

.;D;D;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.4

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.015

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.94

P;.;P;.

Vest4

0.63

MutPred

0.79

Gain of phosphorylation at Y63 (P = 0.1248);.;Gain of phosphorylation at Y63 (P = 0.1248);Gain of phosphorylation at Y63 (P = 0.1248);

MVP

0.39

MPC

2.1

ClinPred

0.92

GERP RS

5.8

Varity_R

0.60

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over