3-40151097-C-T

Variant names:

• chr3-40151097-C-T
• rs199884040
• NM_015460.4:c.382C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001284426.2(MYRIP):​c.-180C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,609,778 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: MYRIP NM_001284426.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44
• Publications: 1 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]

ENTPD3-AS1 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001284426.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	NM_015460.4	MANE Select	c.382C>T	p.Arg128Cys	missense	Exon 4 of 17	NP_056275.2	Q8NFW9-1
	MYRIP	NM_001284426.2		c.-180C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 15	NP_001271355.1	Q8NFW9-4
	MYRIP	NM_001284423.2		c.382C>T	p.Arg128Cys	missense	Exon 4 of 17	NP_001271352.1	Q8NFW9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	ENST00000302541.11	TSL:1 MANE Select	c.382C>T	p.Arg128Cys	missense	Exon 4 of 17	ENSP00000301972.6	Q8NFW9-1
	MYRIP	ENST00000444716.5	TSL:1	c.382C>T	p.Arg128Cys	missense	Exon 4 of 17	ENSP00000398665.1	Q8NFW9-1
	MYRIP	ENST00000396217.7	TSL:1	c.203-11633C>T		intron	N/A	ENSP00000379519.3	Q8NFW9-6

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000130 AC: 32 AN: 246354 AF XY: 0.000143

Gnomad AFR exome AF: 0.0000630

Gnomad AMR exome AF: 0.000210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000554

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000152

Gnomad OTH exome AF: 0.000667

GnomAD4 exome AF: 0.000100 AC: 146 AN: 1457468 Hom.: 1 Cov.: 30 AF XY: 0.000105 AC XY: 76 AN XY: 724854

African (AFR) AF: 0.0000599 AC: 2 AN: 33398

American (AMR) AF: 0.000248 AC: 11 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39534

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.000707 AC: 4 AN: 5656

European-Non Finnish (NFE) AF: 0.0000910 AC: 101 AN: 1109760

Other (OTH) AF: 0.000183 AC: 11 AN: 60200

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74472

African (AFR) AF: 0.0000241 AC: 1 AN: 41568

American (AMR) AF: 0.000392 AC: 6 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000191 Hom.: 0

Bravo AF: 0.000144

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000148 AC: 18

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.4
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.94
MVP		0.94
MPC		0.56
ClinPred		0.93	D
GERP RS		5.1
Varity_R		0.80
gMVP		0.56
Mutation Taster		=252/48	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

dbSNP: rs199884040; hg19: chr3-40192588; COSMIC: COSV56878438;