rs56312827

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_032380.5(GFM2):c.*398_*399delCA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,121,738 control chromosomes in the GnomAD database, including 8,210 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 846 hom., cov: 31)

Exomes 𝑓: 0.12 ( 7364 hom. )

Consequence

GFM2
NM_032380.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.974

Publications

1 publications found

Variant links:

Genes affected

GFM2 (HGNC:29682): (GTP dependent ribosome recycling factor mitochondrial 2) Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors, which is a GTPase that plays a role at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA . Its role in the regulation of normal mitochondrial function and in disease states attributed to mitochondrial dysfunction is not known. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

GFM2 links:

HEXB (HGNC:4879): (hexosaminidase subunit beta) Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

HEXB Gene-Disease associations (from GenCC):

Sandhoff disease
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Myriad Women’s Health

HEXB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 5-74721255-CTG-C is Benign according to our data. Variant chr5-74721255-CTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 354140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFM2	NM_032380.5 link	c.398_399delCA		3_prime_UTR_variant	Exon 21 of 21	ENST00000296805.8	NP_115756.2	Q969S9-1A0A024RAK1
HEXB	NM_000521.4 link	c.82_83delGT		3_prime_UTR_variant	Exon 14 of 14	ENST00000261416.12	NP_000512.2	P07686A0A024RAJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFM2	ENST00000296805.8 link	c.398_399delCA		3_prime_UTR_variant	Exon 21 of 21	1	NM_032380.5	ENSP00000296805.3		Q969S9-1
HEXB	ENST00000261416.12 link	c.82_83delGT		3_prime_UTR_variant	Exon 14 of 14	1	NM_000521.4	ENSP00000261416.7		P07686

Frequencies

GnomAD3 genomes

AF:

0.0945

AC:

14367

AN:

152056

Hom.:

843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.0718

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.0819

GnomAD4 exome

AF:

0.116

AC:

112855

AN:

969564

Hom.:

7364

AF XY:

0.115

AC XY:

57995

AN XY:

502980

show subpopulations

African (AFR)

AF:

0.0202

AC:

466

AN:

23092

American (AMR)

AF:

0.157

AC:

6769

AN:

43088

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

3633

AN:

22968

East Asian (EAS)

AF:

0.158

AC:

5655

AN:

35742

South Asian (SAS)

AF:

0.0772

AC:

5771

AN:

74752

European-Finnish (FIN)

AF:

0.137

AC:

7157

AN:

52222

Middle Eastern (MID)

AF:

0.105

AC:

507

AN:

4810

European-Non Finnish (NFE)

AF:

0.117

AC:

78154

AN:

668894

Other (OTH)

AF:

0.108

AC:

4743

AN:

43996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5159

10319

15478

20638

25797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0945

AC:

14374

AN:

152174

Hom.:

846

Cov.:

AF XY:

0.0952

AC XY:

7084

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0218

AC:

907

AN:

41556

American (AMR)

AF:

0.113

AC:

1728

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

546

AN:

3468

East Asian (EAS)

AF:

0.139

AC:

719

AN:

5180

South Asian (SAS)

AF:

0.0725

AC:

350

AN:

4830

European-Finnish (FIN)

AF:

0.131

AC:

1382

AN:

10548

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8331

AN:

67986

Other (OTH)

AF:

0.0825

AC:

174

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

651

1301

1952

2602

3253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.108

Hom.:

Bravo

AF:

0.0921

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Sandhoff disease

Benign:2

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 16, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.97

Mutation Taster

=99/1

polymorphism (auto)

(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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rs56312827

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over