5-79236825-C-G

Position:

• chr5-79236825-C-G

Variant summary

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

The NM_152405.5(JMY):​c.175C>G​(p.Arg59Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000762 in 1,313,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: JMY NM_152405.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.841

Genes affected

JMY (HGNC:28916): (junction mediating and regulatory protein, p53 cofactor) Predicted to enable Arp2/3 complex binding activity and transcription coactivator activity. Predicted to be involved in several processes, including actin nucleation; intrinsic apoptotic signaling pathway by p53 class mediator; and regulation of transcription, DNA-templated. Located in cell leading edge. [provided by Alliance of Genome Resources, Apr 2022]

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=0.13494602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMY	NM_152405.5	c.175C>G	p.Arg59Gly	missense_variant	1/11	ENST00000396137.5	NP_689618.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMY	ENST00000396137.5	c.175C>G	p.Arg59Gly	missense_variant	1/11	5	NM_152405.5	ENSP00000379441.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.62e-7 AC: 1 AN: 1313018 Hom.: 0 Cov.: 30 AF XY: 0.00000155 AC XY: 1 AN XY: 646552

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.66e-7

Gnomad4 OTH exome AF: 0.00

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

Aug 14, 2024

The c.175C>G (p.R59G) alteration is located in exon 1 (coding exon 1) of the JMY gene. This alteration results from a C to G substitution at nucleotide position 175, causing the arginine (R) at amino acid position 59 to be replaced by a glycine (G). 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	0.20
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.082
Sift	Benign	0.096	T
Sift4G	Uncertain	0.0040	D
Polyphen		0.61	P
Vest4		0.33
MutPred		0.23		Gain of glycosylation at S58 (P = 0.0217);
MVP		0.16
ClinPred		0.83	D
GERP RS		1.8
Varity_R		0.18
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-78532648;