chr3-40044245-G-T

Variant names:

• chr3-40044245-G-T
• NM_015460.4:c.306G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015460.4(MYRIP):​c.306G>T​(p.Trp102Cys) 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 pathogenic outcome for this variant. 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: 10.0
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.306G>T	p.Trp102Cys	missense_variant	Exon 3 of 17	ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.306G>T	p.Trp102Cys	missense_variant	Exon 3 of 17	1	NM_015460.4	ENSP00000301972.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.306G>T (p.W102C) alteration is located in exon 3 (coding exon 2) of the MYRIP gene. This alteration results from a G to T substitution at nucleotide position 306, causing the tryptophan (W) at amino acid position 102 to be replaced by a cysteine (C). 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	0.98
BayesDel_addAF	Benign	-0.00044	T
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	31
DANN	Uncertain	0.99
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.58	D
PhyloP100		10
PROVEAN	Benign	0.22	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.014	D
Sift4G	Benign	0.17	T
Vest4		0.85
MutPred		0.20		Gain of glycosylation at S63 (P = 0.0158);
MVP		0.53
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.92
Mutation Taster		=54/46	polymorphism

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

hg19: chr3-40085736;