Genetic Variant GINM1:p.Cys88Gly (chr6-149572588-T-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_138785.5(GINM1):c.262T>G(p.Cys88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,424,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GINM1
NM_138785.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Publications

0 publications found

Variant links:

Genes affected

GINM1 (HGNC:21074): (glycosylated integral membrane protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GINM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GINM1	NM_138785.5 link	c.262T>G	p.Cys88Gly	missense_variant	Exon 3 of 8	ENST00000367419.10	NP_620140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINM1	ENST00000367419.10 link	c.262T>G	p.Cys88Gly	missense_variant	Exon 3 of 8	1	NM_138785.5	ENSP00000356389.5		Q9NU53
GINM1	ENST00000650599.1 link	n.262T>G		non_coding_transcript_exon_variant	Exon 3 of 8			ENSP00000496902.1		A0A3B3IRL9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1424132

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

710896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32646

American (AMR)

AF:

0.00

AC:

AN:

44108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25836

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078748

Other (OTH)

AF:

0.0000169

AC:

AN:

59050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 12, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.262T>G (p.C88G) alteration is located in exon 3 (coding exon 3) of the GINM1 gene. This alteration results from a T to G substitution at nucleotide position 262, causing the cysteine (C) at amino acid position 88 to be replaced by a glycine (G). 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

0.32

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.12

Eigen

Benign

-0.023

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.64

M_CAP

Benign

0.0040

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

PhyloP100

3.5

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-8.6

REVEL

Benign

0.24

Sift

Benign

0.086

Sift4G

Benign

0.15

Polyphen

0.0050

Vest4

0.61

MutPred

0.74

Loss of sheet (P = 0.0181);

MVP

0.65

MPC

0.32

ClinPred

0.94

GERP RS

4.6

Varity_R

0.64

gMVP

0.72

Mutation Taster

=49/51

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over