3-40055127-G-A

Position:

• chr3-40055127-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.332+10856G>A		intron_variant		ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.332+10856G>A		intron_variant		1	NM_015460.4	ENSP00000301972	P1

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

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.299

Alfa AF: 0.288 Hom.: 11130

Bravo AF: 0.295

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.055
DANN	Benign	0.53

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: rs6599077; hg19: chr3-40096618;