Variant 15-44328772-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_138423.4(GOLM2):c.470G>T(p.Arg157Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,451,348 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: 0.000012 ( 0 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

GOLM2 (HGNC:24892): (golgi membrane protein 2) The increased expression level of this gene is associated with HER-2/neu proto-oncogene overexpression. Amplification and resulting overexpression of this proto-oncogene are found in approximately 30% of human breast and 20% of human ovarian cancers. Alternatively spliced variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Dec 2010]

GOLM2 links:

GOLM2 (HGNC:):

GOLM2 links:

Genome browser will be placed here

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
GOLM2	NM_138423.4 linkuse as main transcript	c.470G>T	p.Arg157Met	missense_variant	3/10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3 linkuse as main transcript	c.470G>T	p.Arg157Met	missense_variant	3/9		NP_816929.1
GOLM2	NR_157849.2 linkuse as main transcript	n.781G>T		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11 linkuse as main transcript	c.470G>T	p.Arg157Met	missense_variant	3/10	1	NM_138423.4	ENSP00000299957.6		Q6P4E1-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1451348

Hom.:

Cov.:

AF XY:

0.00000831

AC XY:

AN XY:

721976

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:

0.0000154

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

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

Dec 21, 2023

The c.470G>T (p.R157M) alteration is located in exon 3 (coding exon 3) of the CASC4 gene. This alteration results from a G to T substitution at nucleotide position 470, causing the arginine (R) at amino acid position 157 to be replaced by a methionine (M). 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

0.43

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.15

T;.;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.90

D;D;T;D

M_CAP

Benign

0.081

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

1.8

.;L;.;L

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.7

D;D;.;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0080

D;D;.;D

Sift4G

Uncertain

0.0070

D;D;.;D

Polyphen

1.0

.;.;.;D

Vest4

0.70, 0.71

MutPred

0.28

.;Loss of methylation at K156 (P = 0.031);.;Loss of methylation at K156 (P = 0.031);

MVP

0.85

MPC

1.2

ClinPred

0.94

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.13

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

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