NM_000851.4:c.*694T>C

Variant names:

• chr1-109718120-T-C
• rs11807
• NM_000851.4:c.*694T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000851.4(GSTM5):​c.*694T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,366 control chromosomes in the GnomAD database, including 2,421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2417 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: GSTM5 NM_000851.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657
• Publications: 43 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

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.*694T>C		3_prime_UTR	Exon 8 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.*694T>C		3_prime_UTR	Exon 8 of 8	ENSP00000256593.3	P46439
	GSTM5	ENST00000966870.1		c.*694T>C		3_prime_UTR	Exon 10 of 10	ENSP00000636929.1
	GSTM5	ENST00000966873.1		c.*694T>C		3_prime_UTR	Exon 8 of 8	ENSP00000636932.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26280 AN: 152032 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.139 AC: 30 AN: 216 Hom.: 4 Cov.: 0 AF XY: 0.156 AC XY: 25 AN XY: 160

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 2 AN: 8

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.128 AC: 23 AN: 180

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.173 AC: 26306 AN: 152150 Hom.: 2417 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74384

African (AFR) AF: 0.121 AC: 5020 AN: 41532

American (AMR) AF: 0.177 AC: 2701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.134 AC: 694 AN: 5186

South Asian (SAS) AF: 0.199 AC: 959 AN: 4820

European-Finnish (FIN) AF: 0.192 AC: 2032 AN: 10578

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13570 AN: 67966

Other (OTH) AF: 0.160 AC: 338 AN: 2108

Alfa AF: 0.188 Hom.: 12296

Bravo AF: 0.168

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.74
DANN	Benign	0.65
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

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: rs11807; hg19: chr1-110260742;