rs199768420

Variant names:

• chr3-40044231-C-A
• rs199768420
• NM_015460.4:c.292C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-40044231-C-A
• chr3-40044231-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015460.4(MYRIP):​c.292C>A​(p.His98Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H98Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.74
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2114276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRIP	NM_015460.4	c.292C>A	p.His98Asn	missense_variant	Exon 3 of 17	ENST00000302541.11	NP_056275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRIP	ENST00000302541.11	c.292C>A	p.His98Asn	missense_variant	Exon 3 of 17	1	NM_015460.4	ENSP00000301972.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.090	T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.069
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	.;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		3.7
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.19	T;T;T
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.14	B;B;.
Vest4		0.36
MutPred		0.31		Gain of ubiquitination at K100 (P = 0.0548);Gain of ubiquitination at K100 (P = 0.0548);Gain of ubiquitination at K100 (P = 0.0548);
MVP		0.75
MPC		0.12
ClinPred		0.84	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.067
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs199768420; hg19: chr3-40085722;