3-40182317-C-T

Position:

• chr3-40182317-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015460.4(MYRIP):​c.971C>T​(p.Pro324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,613,922 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (44 hom.)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.248

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]

EIF1B-AS1 (HGNC:44555): (EIF1B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005500138).
• BP6: Variant 3-40182317-C-T is Benign according to our data. Variant chr3-40182317-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 791475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.971C>T	p.Pro324Leu	missense_variant	9/17	ENST00000302541.11	NP_056275.2
EIF1B-AS1	NR_033965.1	n.537-7595G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.971C>T	p.Pro324Leu	missense_variant	9/17	1	NM_015460.4	ENSP00000301972	P1
EIF1B-AS1	ENST00000657703.1	n.91-64581G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 793 AN: 152152 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00541 AC: 1357 AN: 250990 Hom.: 6 AF XY: 0.00516 AC XY: 700 AN XY: 135662

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.0130

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00210

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.00763

Gnomad OTH exome AF: 0.00704

GnomAD4 exome AF: 0.00632 AC: 9237 AN: 1461652 Hom.: 44 Cov.: 31 AF XY: 0.00621 AC XY: 4516 AN XY: 727124

Gnomad4 AFR exome AF: 0.00102

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00220

Gnomad4 FIN exome AF: 0.00305

Gnomad4 NFE exome AF: 0.00704

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.00521 AC: 793 AN: 152270 Hom.: 7 Cov.: 32 AF XY: 0.00500 AC XY: 372 AN XY: 74440

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00773

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00671 Hom.: 7

Bravo AF: 0.00558

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.00597 AC: 23

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.00884 AC: 76

ExAC AF: 0.00548 AC: 665

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00960

EpiControl AF: 0.00949

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2022	MYRIP: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.6
DANN	Benign	0.41
DEOGEN2	Benign	0.014	T;T;.;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.63	.;T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0055	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.83	L;L;.;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.066
Sift	Benign	0.40	T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.0080	B;B;.;.;.
Vest4		0.056
MVP		0.44
MPC		0.11
ClinPred		0.0022	T
GERP RS		1.0
Varity_R		0.030
gMVP		0.064

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: rs144807590; hg19: chr3-40223808;