rs9985399

Variant names:

• chr3-39967143-T-C
• rs9985399
• NM_015460.4:c.110+66217T>C

Variant summary

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

The NM_015460.4(MYRIP):​c.110+66217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,162 control chromosomes in the GnomAD database, including 5,068 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 0.19 (5068 hom., cov: 32)
• Consequence: MYRIP NM_015460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.110+66217T>C		intron_variant	Intron 2 of 16	ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.110+66217T>C		intron_variant	Intron 2 of 16	1	NM_015460.4	ENSP00000301972.6

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28279 AN: 152044 Hom.: 5039 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0733

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.186 AC: 28360 AN: 152162 Hom.: 5068 Cov.: 32 AF XY: 0.185 AC XY: 13743 AN XY: 74404

African (AFR) AF: 0.462 AC: 19158 AN: 41474

American (AMR) AF: 0.0911 AC: 1393 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0733 AC: 254 AN: 3464

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5156

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4828

European-Finnish (FIN) AF: 0.0733 AC: 778 AN: 10610

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0569 AC: 3872 AN: 68026

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.0997 Hom.: 6760

Bravo AF: 0.200

Asia WGS AF: 0.252 AC: 878 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs9985399; hg19: chr3-40008634;