NM_000851.4:c.234C>G

Variant names:

• chr1-109713540-C-G
• rs144839885
• NM_000851.4:c.234C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_000851.4(GSTM5):​c.234C>G​(p.Arg78Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,613,106 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (75 hom.)
• Consequence: GSTM5 NM_000851.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.29
• Publications: 2 publications found

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP6: Variant 1-109713540-C-G is Benign according to our data. Variant chr1-109713540-C-G is described in ClinVar as Benign. ClinVar VariationId is 784446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00585 (885/151252) while in subpopulation SAS AF = 0.019 (91/4796). AF 95% confidence interval is 0.0158. There are 6 homozygotes in GnomAd4. There are 441 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000851.4. 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
	GSTM5	NM_000851.4	MANE Select	c.234C>G	p.Arg78Arg	synonymous	Exon 4 of 8	NP_000842.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM5	ENST00000256593.8	TSL:1 MANE Select	c.234C>G	p.Arg78Arg	synonymous	Exon 4 of 8	ENSP00000256593.3	P46439
	GSTM5	ENST00000878690.1		c.234C>G	p.Arg78Arg	synonymous	Exon 4 of 9	ENSP00000548749.1
	GSTM5	ENST00000966870.1		c.234C>G	p.Arg78Arg	synonymous	Exon 5 of 10	ENSP00000636929.1

Frequencies

GnomAD3 genomes AF: 0.00584 AC: 882 AN: 151134 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00315

Gnomad AMI AF: 0.00774

Gnomad AMR AF: 0.00514

Gnomad ASJ AF: 0.00809

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0185

Gnomad FIN AF: 0.00805

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00650

Gnomad OTH AF: 0.00962

GnomAD2 exomes AF: 0.00755 AC: 1900 AN: 251492 AF XY: 0.00845

Gnomad AFR exome AF: 0.00314

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.00962

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00979

Gnomad NFE exome AF: 0.00592

Gnomad OTH exome AF: 0.00814

GnomAD4 exome AF: 0.00598 AC: 8742 AN: 1461854 Hom.: 75 Cov.: 34 AF XY: 0.00668 AC XY: 4861 AN XY: 727224

African (AFR) AF: 0.00257 AC: 86 AN: 33478

American (AMR) AF: 0.00362 AC: 162 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00934 AC: 244 AN: 26136

East Asian (EAS) AF: 0.000781 AC: 31 AN: 39700

South Asian (SAS) AF: 0.0230 AC: 1983 AN: 86258

European-Finnish (FIN) AF: 0.00944 AC: 504 AN: 53418

Middle Eastern (MID) AF: 0.0170 AC: 98 AN: 5768

European-Non Finnish (NFE) AF: 0.00469 AC: 5214 AN: 1111978

Other (OTH) AF: 0.00695 AC: 420 AN: 60396

GnomAD4 genome AF: 0.00585 AC: 885 AN: 151252 Hom.: 6 Cov.: 33 AF XY: 0.00597 AC XY: 441 AN XY: 73922

African (AFR) AF: 0.00316 AC: 130 AN: 41122

American (AMR) AF: 0.00513 AC: 78 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00809 AC: 28 AN: 3462

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5162

South Asian (SAS) AF: 0.0190 AC: 91 AN: 4796

European-Finnish (FIN) AF: 0.00805 AC: 85 AN: 10554

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00650 AC: 440 AN: 67650

Other (OTH) AF: 0.00951 AC: 20 AN: 2102

Alfa AF: 0.00724 Hom.: 3

Bravo AF: 0.00530

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.00818

EpiControl AF: 0.00735

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.78
PhyloP100		1.3
PromoterAI		-0.018	Neutral
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs144839885; hg19: chr1-110256162; COSMIC: COSV56658921; COSMIC: COSV56658921;