15-44328752-C-A

Position:

• chr15-44328752-C-A

Variant summary

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

The NM_138423.4(GOLM2):​c.450C>A​(p.Asn150Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: GOLM2 NM_138423.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.303

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 (HGNC:):

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=0.40870324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLM2	NM_138423.4	c.450C>A	p.Asn150Lys	missense_variant	3/10	ENST00000299957.11	NP_612432.2
GOLM2	NM_177974.3	c.450C>A	p.Asn150Lys	missense_variant	3/9		NP_816929.1
GOLM2	NR_157849.2	n.761C>A		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLM2	ENST00000299957.11	c.450C>A	p.Asn150Lys	missense_variant	3/10	1	NM_138423.4	ENSP00000299957.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.450C>A (p.N150K) alteration is located in exon 3 (coding exon 3) of the CASC4 gene. This alteration results from a C to A substitution at nucleotide position 450, causing the asparagine (N) at amino acid position 150 to be replaced by a lysine (K). 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	0.84
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;.;.;.
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.41	T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.4	.;M;.;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.5	D;D;.;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0070	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;.;D
Polyphen		1.0	.;.;.;D
Vest4		0.87, 0.87
MutPred		0.19		.;Gain of ubiquitination at N150 (P = 0.0238);.;Gain of ubiquitination at N150 (P = 0.0238);
MVP		0.80
MPC		1.3
ClinPred		1.0	D
GERP RS		-0.38
gMVP		0.31

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: chr15-44620950;