3-39913575-A-C

Position:

• chr3-39913575-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015460.4(MYRIP):​c.110+12649A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,980 control chromosomes in the GnomAD database, including 19,121 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 0.49 (19121 hom., cov: 32)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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]

MYRIP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.110+12649A>C		intron_variant		ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.110+12649A>C		intron_variant		1	NM_015460.4	ENSP00000301972.6

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74021 AN: 151862 Hom.: 19078 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.488 AC: 74131 AN: 151980 Hom.: 19121 Cov.: 32 AF XY: 0.486 AC XY: 36110 AN XY: 74278

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.482

Alfa AF: 0.474 Hom.: 2685

Bravo AF: 0.501

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.51

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: rs1599903; hg19: chr3-39955066;