3-40044269-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000396217.7(MYRIP):c.200G>A(p.Arg67Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,990 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (9 hom.)
• Consequence: MYRIP ENST00000396217.7 missense, splice_region
• Scores: Splicing: ADA: 0.000001669
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0220

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00632897).
• BP6: Variant 3-40044269-G-A is Benign according to our data. Variant chr3-40044269-G-A is described in ClinVar as [Benign]. Clinvar id is 771852.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-40044269-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4	c.330G>A	p.Ala110=	splice_region_variant, synonymous_variant	3/17	ENST00000302541.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11	c.330G>A	p.Ala110=	splice_region_variant, synonymous_variant	3/17	1	NM_015460.4	P1

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 256 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00216 AC: 539 AN: 249996 Hom.: 0 AF XY: 0.00243 AC XY: 329 AN XY: 135202

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00389

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00199

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00246 AC: 3593 AN: 1461662 Hom.: 9 Cov.: 31 AF XY: 0.00248 AC XY: 1806 AN XY: 727156

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.00244

Gnomad4 ASJ exome AF: 0.00402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00217

Gnomad4 FIN exome AF: 0.000730

Gnomad4 NFE exome AF: 0.00263

Gnomad4 OTH exome AF: 0.00242

GnomAD4 genome AF: 0.00169 AC: 257 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.00168 AC XY: 125 AN XY: 74500

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00262

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00226 Hom.: 0

Bravo AF: 0.00171

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00216 AC: 262

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00354

EpiControl AF: 0.00439

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	6.4
Dann	Benign	0.90
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;N
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.034
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.38	T
Vest4		0.22
MVP		0.15
ClinPred		0.011	T
GERP RS		-11

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000017
dbscSNV1_RF	Benign	0.058
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: rs56248790; hg19: chr3-40085760;