20-34978087-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020884.7(MYH7B):c.82C>A(p.Pro28Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,613,986 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P28P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.025 (159 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (156 hom.)
• Consequence: MYH7B NM_020884.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.170

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016455948).
• BP6: Variant 20-34978087-C-A is Benign according to our data. Variant chr20-34978087-C-A is described in ClinVar as [Benign]. Clinvar id is 777541.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH7B	NM_020884.7	c.82C>A	p.Pro28Thr	missense_variant	5/45	ENST00000262873.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH7B	ENST00000262873.13	c.82C>A	p.Pro28Thr	missense_variant	5/45	1	NM_020884.7	P1
MYH7B	ENST00000470929.5	n.168C>A		non_coding_transcript_exon_variant	2/6	2
MYH7B	ENST00000673749.1	n.616C>A		non_coding_transcript_exon_variant	5/9

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3794 AN: 152104 Hom.: 158 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00621 AC: 1547 AN: 249270 Hom.: 65 AF XY: 0.00501 AC XY: 677 AN XY: 135258

Gnomad AFR exome AF: 0.0897

Gnomad AMR exome AF: 0.00316

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.00330

GnomAD4 exome AF: 0.00266 AC: 3882 AN: 1461764 Hom.: 156 Cov.: 32 AF XY: 0.00244 AC XY: 1771 AN XY: 727194

Gnomad4 AFR exome AF: 0.0943

Gnomad4 AMR exome AF: 0.00418

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00555

GnomAD4 genome AF: 0.0250 AC: 3806 AN: 152222 Hom.: 159 Cov.: 32 AF XY: 0.0242 AC XY: 1798 AN XY: 74426

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.00785

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00399 Hom.: 37

Bravo AF: 0.0285

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0803 AC: 348

ESP6500EA AF: 0.000469 AC: 4

ExAC AF: 0.00760 AC: 921

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	15
Dann	Uncertain	0.98
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.34	N
LIST_S2	Uncertain	0.86	D;D
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	0.64	D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D;.
Sift4G	Uncertain	0.0090	D;D
Vest4		0.16
MVP		0.25
MPC		0.18
ClinPred		0.053	T
GERP RS		0.38
Varity_R		0.094
gMVP		0.35

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

LitVar

Other links and lift over

dbSNP: rs17092199; hg19: chr20-33565890;