3-40190032-C-T

Position:

• chr3-40190032-C-T

Variant summary

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

The NM_015460.4(MYRIP):​c.1234C>T​(p.Pro412Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P412T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRIP NM_015460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33

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=0.17738569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRIP	NM_015460.4	c.1234C>T	p.Pro412Ser	missense_variant	10/17	ENST00000302541.11
EIF1B-AS1	NR_033965.1	n.537-15310G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRIP	ENST00000302541.11	c.1234C>T	p.Pro412Ser	missense_variant	10/17	1	NM_015460.4	P1
EIF1B-AS1	ENST00000657703.1	n.91-72296G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Apr 06, 2024

The c.1234C>T (p.P412S) alteration is located in exon 10 (coding exon 9) of the MYRIP gene. This alteration results from a C to T substitution at nucleotide position 1234, causing the proline (P) at amino acid position 412 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	0.098
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;.;.;.
Eigen	Benign	0.16
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	.;D;D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;.;M;.
MutationTaster	Benign	0.98	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.44	N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.088	T;T;T;T;T
Sift4G	Benign	0.75	T;T;T;T;T
Polyphen		0.90	P;P;.;.;.
Vest4		0.18
MutPred		0.099		Gain of glycosylation at S414 (P = 0.0169);Gain of glycosylation at S414 (P = 0.0169);.;Gain of glycosylation at S414 (P = 0.0169);.;
MVP		0.52
MPC		0.44
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.061
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-40231523;