Variant chr15-44328714-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138423.4(GOLM2):c.412C>T(p.Leu138Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,613,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04870391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GOLM2	NM_138423.4 linkuse as main transcript	c.412C>T	p.Leu138Phe	missense_variant	3/10	ENST00000299957.11
GOLM2	NM_177974.3 linkuse as main transcript	c.412C>T	p.Leu138Phe	missense_variant	3/9
GOLM2	NR_157849.2 linkuse as main transcript	n.723C>T		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLM2	ENST00000299957.11 linkuse as main transcript	c.412C>T	p.Leu138Phe	missense_variant	3/10	1	NM_138423.4	P3	Q6P4E1-4

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000104

AC:

AN:

250276

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1460840

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726694

show subpopulations

Gnomad4 AFR exome

AF:

0.000987

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000223

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000337

Hom.:

Bravo

AF:

0.000393

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

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

Sep 13, 2023

The c.412C>T (p.L138F) alteration is located in exon 3 (coding exon 3) of the CASC4 gene. This alteration results from a C to T substitution at nucleotide position 412, causing the leucine (L) at amino acid position 138 to be replaced by a phenylalanine (F). 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

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;.;.;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.063

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Uncertain

0.47

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.9

N;N;.;N

Sift

Uncertain

0.022

D;T;.;T

Sift4G

Uncertain

0.017

D;T;.;D

Polyphen

1.0

.;.;.;D

Vest4

0.36, 0.44

MVP

0.83

MPC

0.90

ClinPred

0.045

GERP RS

6.0

gMVP

0.033

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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