rs138774955

Variant names:

• chr3-40151107-G-A
• rs138774955
• NM_015460.4:c.392G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-40151107-G-A
• chr3-40151107-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015460.4(MYRIP):​c.392G>A​(p.Arg131His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,610,474 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.43
• 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]

ENTPD3-AS1 (HGNC:):

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015460.4. 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.392G>A	p.Arg131His	missense	Exon 4 of 17	NP_056275.2	Q8NFW9-1
	MYRIP	NM_001284423.2		c.392G>A	p.Arg131His	missense	Exon 4 of 17	NP_001271352.1	Q8NFW9-1
	MYRIP	NM_001284424.2		c.392G>A	p.Arg131His	missense	Exon 4 of 16	NP_001271353.1	Q8NFW9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	ENST00000302541.11	TSL:1 MANE Select	c.392G>A	p.Arg131His	missense	Exon 4 of 17	ENSP00000301972.6	Q8NFW9-1
	MYRIP	ENST00000444716.5	TSL:1	c.392G>A	p.Arg131His	missense	Exon 4 of 17	ENSP00000398665.1	Q8NFW9-1
	MYRIP	ENST00000396217.7	TSL:1	c.203-11623G>A		intron	N/A	ENSP00000379519.3	Q8NFW9-6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 247436 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000898

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000206 AC: 30 AN: 1458288 Hom.: 0 Cov.: 30 AF XY: 0.0000262 AC XY: 19 AN XY: 725286

African (AFR) AF: 0.0000598 AC: 2 AN: 33418

American (AMR) AF: 0.0000451 AC: 2 AN: 44346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.0000351 AC: 3 AN: 85490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5640

European-Non Finnish (NFE) AF: 0.0000198 AC: 22 AN: 1110208

Other (OTH) AF: 0.0000166 AC: 1 AN: 60246

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

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	Benign	0.16
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.9	L
PhyloP100		9.4
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.47
MVP		0.87
MPC		0.58
ClinPred		0.85	D
GERP RS		5.8
Varity_R		0.44
gMVP		0.20
Mutation Taster		=70/30	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: rs138774955; hg19: chr3-40192598; COSMIC: COSV105879683;