chr3-40055127-G-A

Variant names:

• chr3-40055127-G-A
• rs6599077
• NM_015460.4:c.332+10856G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015460.4(MYRIP):​c.332+10856G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,002 control chromosomes in the GnomAD database, including 6,517 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6517 hom., cov: 32)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	NM_015460.4	MANE Select	c.332+10856G>A		intron	N/A	NP_056275.2
	MYRIP	NM_001284423.2		c.332+10856G>A		intron	N/A	NP_001271352.1
	MYRIP	NM_001284424.2		c.332+10856G>A		intron	N/A	NP_001271353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRIP	ENST00000302541.11	TSL:1 MANE Select	c.332+10856G>A		intron	N/A	ENSP00000301972.6
	MYRIP	ENST00000444716.5	TSL:1	c.332+10856G>A		intron	N/A	ENSP00000398665.1
	MYRIP	ENST00000396217.7	TSL:1	c.202+10856G>A		intron	N/A	ENSP00000379519.3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44238 AN: 151884 Hom.: 6518 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44256 AN: 152002 Hom.: 6517 Cov.: 32 AF XY: 0.292 AC XY: 21663 AN XY: 74282

African (AFR) AF: 0.296 AC: 12291 AN: 41456

American (AMR) AF: 0.292 AC: 4456 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1366 AN: 3470

East Asian (EAS) AF: 0.356 AC: 1838 AN: 5166

South Asian (SAS) AF: 0.325 AC: 1566 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2820 AN: 10546

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.278 AC: 18907 AN: 67966

Other (OTH) AF: 0.299 AC: 630 AN: 2106

Alfa AF: 0.290 Hom.: 18267

Bravo AF: 0.295

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.055
DANN	Benign	0.53
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs6599077; hg19: chr3-40096618;