3-40151083-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015460.4(MYRIP):c.368A>G(p.Asn123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,758 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26001292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4	c.368A>G	p.Asn123Ser	missense_variant	4/17	ENST00000302541.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11	c.368A>G	p.Asn123Ser	missense_variant	4/17	1	NM_015460.4	P1
EIF1B-AS1	ENST00000657703.1	n.91-33347T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456758 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

The c.368A>G (p.N123S) alteration is located in exon 4 (coding exon 3) of the MYRIP gene. This alteration results from a A to G substitution at nucleotide position 368, causing the asparagine (N) at amino acid position 123 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	14
Dann	Uncertain	0.99
DEOGEN2	Benign	0.29	T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.29
MutPred		0.42		Gain of glycosylation at Y122 (P = 0.0553);Gain of glycosylation at Y122 (P = 0.0553);Gain of glycosylation at Y122 (P = 0.0553);
MVP		0.76
MPC		0.083
ClinPred		0.77	D
GERP RS		3.6
Varity_R		0.14
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-40192574;