2-31932104-C-A

Variant names:

• chr2-31932104-C-A
• rs1664251209
• NM_001301833.4:c.175G>T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.59

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEMO1	NM_001301833.4	c.175G>T	p.Ala59Ser	missense_variant	Exon 4 of 10	ENST00000404530.6	NP_001288762.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEMO1	ENST00000404530.6	c.175G>T	p.Ala59Ser	missense_variant	Exon 4 of 10	2	NM_001301833.4	ENSP00000385557.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461376 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727010

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.: 31

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
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	D
LIST_S2	Pathogenic	0.98	.;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.4	M;.;M;.
PrimateAI	Uncertain	0.75	T
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	D
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

Other links and lift over

dbSNP: rs1664251209; hg19: chr2-32157173;