chr15-44337776-A-C

Variant names:

• chr15-44337776-A-C
• rs374515571
• NM_138423.4:c.590A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138423.4(GOLM2):​c.590A>C​(p.Lys197Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,428,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K197R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: GOLM2 NM_138423.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16832939).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138423.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	NM_138423.4	MANE Select	c.590A>C	p.Lys197Thr	missense	Exon 5 of 10	NP_612432.2
	GOLM2	NM_177974.3		c.590A>C	p.Lys197Thr	missense	Exon 5 of 9	NP_816929.1	Q6P4E1-2
	GOLM2	NR_157849.2		n.901A>C		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.590A>C	p.Lys197Thr	missense	Exon 5 of 10	ENSP00000299957.6	Q6P4E1-4
	GOLM2	ENST00000345795.6	TSL:1	c.590A>C	p.Lys197Thr	missense	Exon 5 of 9	ENSP00000335063.4	Q6P4E1-2
	GOLM2	ENST00000557945.5	TSL:1	n.499A>C		non_coding_transcript_exon	Exon 4 of 6	ENSP00000453720.1	Q6P4E1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000138 AC: 3 AN: 217474 AF XY: 0.0000253

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000852

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000953

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 23 AN: 1428082 Hom.: 0 Cov.: 30 AF XY: 0.0000211 AC XY: 15 AN XY: 710234

African (AFR) AF: 0.00 AC: 0 AN: 31104

American (AMR) AF: 0.0000602 AC: 2 AN: 33228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24796

East Asian (EAS) AF: 0.00 AC: 0 AN: 38486

South Asian (SAS) AF: 0.00 AC: 0 AN: 79386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.0000190 AC: 21 AN: 1103194

Other (OTH) AF: 0.00 AC: 0 AN: 59028

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000165 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.060	T
Polyphen		0.98	D
Vest4		0.20
MVP		0.83
MPC		1.0
ClinPred		0.45	T
GERP RS		5.0
PromoterAI		-0.0025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs374515571; hg19: chr15-44629974;