chr2-210298474-T-G

Position:

• chr2-210298474-T-G

Variant summary

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

The NM_079420.3(MYL1):​c.250A>C​(p.Thr84Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL1 NM_079420.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.20

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

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=0.39860544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.250A>C	p.Thr84Pro	missense_variant	3/7	ENST00000352451.4
MYL1	NM_079422.3	c.118A>C	p.Thr40Pro	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.250A>C	p.Thr84Pro	missense_variant	3/7	1	NM_079420.3
MYL1	ENST00000341685.8	c.118A>C	p.Thr40Pro	missense_variant	3/7	1		P1
MYL1	ENST00000484290.1	n.381A>C		non_coding_transcript_exon_variant	4/6	5
MYL1	ENST00000496436.5	n.353A>C		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Mar 29, 2023

The c.250A>C (p.T84P) alteration is located in exon 3 (coding exon 3) of the MYL1 gene. This alteration results from a A to C substitution at nucleotide position 250, causing the threonine (T) at amino acid position 84 to be replaced by a proline (P). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.47	T;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.77	.;N
MutationTaster	Benign	0.71	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.53	N;N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		0.58	P;P
Vest4		0.47
MutPred		0.55		.;Loss of catalytic residue at T84 (P = 0.0342);
MVP		0.83
MPC		0.37
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.30
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-211163198;