20-34956272-C-G

Variant names:

• chr20-34956272-C-G
• rs3761144
• NM_020884.7:c.-337+265C>G

Variant summary

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

The NM_020884.7(MYH7B):​c.-337+265C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 151,936 control chromosomes in the GnomAD database, including 30,469 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 0.62 (30469 hom., cov: 31)
• Consequence: MYH7B NM_020884.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547
• Publications: 21 publications found

Genes affected

MYH7B (HGNC:15906): (myosin heavy chain 7B) The myosin II molecule is a multi-subunit complex consisting of two heavy chains and four light chains. This gene encodes a heavy chain of myosin II, which is a member of the motor-domain superfamily. The heavy chain includes a globular motor domain, which catalyzes ATP hydrolysis and interacts with actin, and a tail domain in which heptad repeat sequences promote dimerization by interacting to form a rod-like alpha-helical coiled coil. This heavy chain subunit is a slow-twitch myosin. Alternatively spliced transcript variants have been found, but the full-length nature of these variants is not determined. [provided by RefSeq, Mar 2010]

GSS (HGNC:4624): (glutathione synthetase) Glutathione is important for a variety of biological functions, including protection of cells from oxidative damage by free radicals, detoxification of xenobiotics, and membrane transport. The protein encoded by this gene functions as a homodimer to catalyze the second step of glutathione biosynthesis, which is the ATP-dependent conversion of gamma-L-glutamyl-L-cysteine to glutathione. Defects in this gene are a cause of glutathione synthetase deficiency. [provided by RefSeq, Jul 2008]

GSS Gene-Disease associations (from GenCC):

• inherited glutathione synthetase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• glutathione synthetase deficiency with 5-oxoprolinuria

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7B	NM_020884.7	c.-337+265C>G		intron_variant	Intron 1 of 44	ENST00000262873.13	NP_065935.4
GSS	NM_001322494.1	c.-411G>C		upstream_gene_variant			NP_001309423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7B	ENST00000262873.13	c.-337+265C>G		intron_variant	Intron 1 of 44	1	NM_020884.7	ENSP00000262873.8
MYH7B	ENST00000673749.1	n.198+265C>G		intron_variant	Intron 1 of 8
GSS	ENST00000643188.1	c.-411G>C		upstream_gene_variant				ENSP00000493903.1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94746 AN: 151818 Hom.: 30440 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.581

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.624 AC: 94806 AN: 151936 Hom.: 30469 Cov.: 31 AF XY: 0.621 AC XY: 46106 AN XY: 74264

African (AFR) AF: 0.763 AC: 31598 AN: 41412

American (AMR) AF: 0.445 AC: 6791 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2097 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2333 AN: 5174

South Asian (SAS) AF: 0.710 AC: 3413 AN: 4810

European-Finnish (FIN) AF: 0.583 AC: 6143 AN: 10542

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40624 AN: 67946

Other (OTH) AF: 0.585 AC: 1235 AN: 2110

Alfa AF: 0.519 Hom.: 1565

Bravo AF: 0.611

Asia WGS AF: 0.596 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.32
PhyloP100		0.55
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3761144; hg19: chr20-33544075;