3-39900885-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015460.4(MYRIP):c.69A>T(p.Gln23His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

Genes affected

MYRIP (HGNC:19156): (myosin VIIA and Rab interacting protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be involved in positive regulation of insulin secretion. Predicted to be located in actin cytoskeleton; dense core granule; and perinuclear region of cytoplasm. Predicted to be part of exocyst. Predicted to be active in cortical actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4	c.69A>T	p.Gln23His	missense_variant	2/17	ENST00000302541.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11	c.69A>T	p.Gln23His	missense_variant	2/17	1	NM_015460.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Jan 24, 2023

The c.69A>T (p.Q23H) alteration is located in exon 2 (coding exon 1) of the MYRIP gene. This alteration results from a A to T substitution at nucleotide position 69, causing the glutamine (Q) at amino acid position 23 to be replaced by a histidine (H). 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	0.78
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;D;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.078
FATHMM_MKL	Benign	0.56	D
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Uncertain	0.0071	D
MutationAssessor	Uncertain	2.5	M;M;M
MutationTaster	Benign	0.92	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.0	D;D;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.55
MutPred		0.23		Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);
MVP		0.72
MPC		0.50
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.57
gMVP		0.47

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: chr3-39942376;