Genetic Variant NM_138423.4:c.835C>T (chr15-44379722-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_138423.4(GOLM2):c.835C>T(p.His279Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000647 in 1,469,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

GOLM2
NM_138423.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015815377).

BP6

Variant 15-44379722-C-T is Benign according to our data. Variant chr15-44379722-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2471371.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLM2	NM_138423.4	MANE Select	c.835C>T	p.His279Tyr	missense	Exon 7 of 10	NP_612432.2
GOLM2	NM_177974.3		c.835C>T	p.His279Tyr	missense	Exon 7 of 9	NP_816929.1	Q6P4E1-2
GOLM2	NR_157849.2		n.2538C>T		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLM2	ENST00000299957.11	TSL:1 MANE Select	c.835C>T	p.His279Tyr	missense	Exon 7 of 10	ENSP00000299957.6	Q6P4E1-4
GOLM2	ENST00000345795.6	TSL:1	c.835C>T	p.His279Tyr	missense	Exon 7 of 9	ENSP00000335063.4	Q6P4E1-2
GOLM2	ENST00000915850.1		c.820C>T	p.His274Tyr	missense	Exon 7 of 10	ENSP00000585909.1

Frequencies

GnomAD3 genomes

AF:

0.000336

AC:

AN:

145728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00124

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:

0.00

GnomAD2 exomes

AF:

0.0000836

AC:

AN:

251178

AF XY:

0.0000884

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000348

AC:

AN:

1323518

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

657100

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

29148

American (AMR)

AF:

0.0000743

AC:

AN:

40362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20950

East Asian (EAS)

AF:

0.00

AC:

AN:

28940

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42224

Middle Eastern (MID)

AF:

0.000206

AC:

AN:

4866

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021166

Other (OTH)

AF:

0.000118

AC:

AN:

50936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000336

AC:

AN:

145842

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

70742

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

39720

American (AMR)

AF:

0.00

AC:

AN:

14218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4674

South Asian (SAS)

AF:

0.00

AC:

AN:

4332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66796

Other (OTH)

AF:

0.00

AC:

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000882

Hom.:

Bravo

AF:

0.000351

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Benign

0.81

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.24

M_CAP

Benign

0.026

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.85

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

REVEL

Benign

0.17

Sift

Benign

0.94

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.13

MVP

0.59

MPC

0.49

ClinPred

0.0069

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.15

Mutation Taster

=81/19

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over