7-101613572-A-T

Position:

• chr7-101613572-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000223167.5(MYL10):​c.584T>A​(p.Val195Asp) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL10 ENST00000223167.5 missense, splice_region
• Scores: Splicing: ADA: 0.00004344
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.70

Genes affected

MYL10 (HGNC:29825): (myosin light chain 10) Predicted to enable calcium ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL10	NM_138403.5	c.584T>A	p.Val195Asp	missense_variant, splice_region_variant	8/8	ENST00000223167.5	NP_612412.2
MYL10	XM_017012793.2	c.347T>A	p.Val116Asp	missense_variant, splice_region_variant	7/7		XP_016868282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL10	ENST00000223167.5	c.584T>A	p.Val195Asp	missense_variant, splice_region_variant	8/8	1	NM_138403.5	ENSP00000223167
MYL10	ENST00000642629.2	c.407T>A	p.Val136Asp	missense_variant, splice_region_variant	7/7			ENSP00000493793	P1
MYL10	ENST00000706943.1	c.347T>A	p.Val116Asp	missense_variant, splice_region_variant	7/7			ENSP00000516663

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 15, 2024

The c.584T>A (p.V195D) alteration is located in exon 8 (coding exon 8) of the MYL10 gene. This alteration results from a T to A substitution at nucleotide position 584, causing the valine (V) at amino acid position 195 to be replaced by an aspartic acid (D). 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	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.61	D;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Pathogenic	3.2	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-5.7	D;.
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.97	D;.
Vest4		0.55
MutPred		0.70		Gain of disorder (P = 0.018);.;
MVP		0.85
MPC		0.31
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.75
gMVP		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000043
dbscSNV1_RF	Benign	0.058
SpliceAI score (max)		0.060		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: chr7-101256852;