3-40182279-G-T

Variant names:

• chr3-40182279-G-T
• rs1259914372
• NM_015460.4:c.933G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015460.4(MYRIP):​c.933G>T​(p.Glu311Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.46

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]

EIF1B-AS1 (HGNC:):

EIF1B-AS1 (HGNC:44555): (EIF1B antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15835014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.933G>T	p.Glu311Asp	missense_variant	Exon 9 of 17	ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.933G>T	p.Glu311Asp	missense_variant	Exon 9 of 17	1	NM_015460.4	ENSP00000301972.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

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 Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152122 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74302

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.933G>T (p.E311D) alteration is located in exon 9 (coding exon 8) of the MYRIP gene. This alteration results from a G to T substitution at nucleotide position 933, causing the glutamic acid (E) at amino acid position 311 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	Benign	0.085
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;.;.;.
Eigen	Benign	0.080
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.62	.;T;T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;M;.;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.070	N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.075	T;T;T;T;T
Sift4G	Benign	0.58	T;T;T;T;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.061
MutPred		0.11		Gain of glycosylation at T307 (P = 0.0291);Gain of glycosylation at T307 (P = 0.0291);.;Gain of glycosylation at T307 (P = 0.0291);.;
MVP		0.61
MPC		0.14
ClinPred		0.33	T
GERP RS		3.4
Varity_R		0.044
gMVP		0.045

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

LitVar

Other links and lift over

dbSNP: rs1259914372; hg19: chr3-40223770;