20-34977658-C-T

Variant names:

• chr20-34977658-C-T
• rs868124121
• NM_020884.7:c.-95C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_Moderate BS2_Supporting

The NM_020884.7(MYH7B):​c.-95C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000379 in 1,583,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MYH7B NM_020884.7 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38
• Publications: 1 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]

MYH7B Gene-Disease associations (from GenCC):

• left ventricular noncompaction

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22727787).
• BS2: High AC in GnomAdExome4 at 5 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020884.7. 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
	MYH7B	NM_020884.7	MANE Select	c.-95C>T		5_prime_UTR	Exon 4 of 45	NP_065935.4	A7E2Y1-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH7B	ENST00000262873.13	TSL:1 MANE Select	c.-95C>T		5_prime_UTR	Exon 4 of 45	ENSP00000262873.8	A7E2Y1-4
	MYH7B	ENST00000971120.1		c.-33C>T		5_prime_UTR	Exon 1 of 41	ENSP00000641179.1
	MYH7B	ENST00000673749.1		n.440C>T		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes AF: 0.00000662 AC: 1 AN: 151104 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1432090 Hom.: 0 Cov.: 31 AF XY: 0.00000423 AC XY: 3 AN XY: 708944

African (AFR) AF: 0.000150 AC: 5 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 39638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25454

East Asian (EAS) AF: 0.00 AC: 0 AN: 38790

South Asian (SAS) AF: 0.00 AC: 0 AN: 81510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096928

Other (OTH) AF: 0.00 AC: 0 AN: 59366

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151222 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 73878

African (AFR) AF: 0.0000243 AC: 1 AN: 41194

American (AMR) AF: 0.00 AC: 0 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67822

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.51	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.18	T
PhyloP100		3.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.12	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Vest4		0.31
MutPred		0.25		Loss of disorder (P = 0.0017)
MVP		0.61
MPC		0.16
ClinPred		0.75	D
GERP RS		4.5
PromoterAI		-0.17	Neutral
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

Other links and lift over

dbSNP: rs868124121; hg19: chr20-33565461;