20-34977634-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020884.7(MYH7B):c.-119G>T variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH7B NM_020884.7 splice_region, 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2694487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7B	NM_020884.7	c.-119G>T		splice_region_variant, 5_prime_UTR_variant	4/45	ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.-119G>T		splice_region_variant, 5_prime_UTR_variant	4/45	1	NM_020884.7	P1
MYH7B	ENST00000673749.1	n.416G>T		splice_region_variant, non_coding_transcript_exon_variant	4/9
MYH7B	ENST00000470929.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1423880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2023

The c.8G>T (p.G3V) alteration is located in exon 4 (coding exon 2) of the MYH7B gene. This alteration results from a G to T substitution at nucleotide position 8, causing the glycine (G) at amino acid position 3 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	13
Dann	Uncertain	0.98
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Uncertain	-0.0095	T
MutationTaster	Benign	0.83	D
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.14	N;.
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D;.
Vest4		0.26
MutPred		0.11		Gain of sheet (P = 0.0507);.;
MVP		0.75
MPC		0.72
ClinPred		0.36	T
GERP RS		0.91
Varity_R		0.064
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-33565437; COSMIC: COSV53424273; COSMIC: COSV53424273;