chr5-79314351-A-G

Position:

• chr5-79314351-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152405.5(JMY):​c.2159A>G​(p.His720Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,614,118 control chromosomes in the GnomAD database, including 1,544 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.056 (543 hom., cov: 32)
  • Exomes 𝑓: 0.021 (1001 hom.)
• Consequence: JMY NM_152405.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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]

JMY (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013534129).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMY	NM_152405.5	c.2159A>G	p.His720Arg	missense_variant	9/11	ENST00000396137.5	NP_689618.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMY	ENST00000396137.5	c.2159A>G	p.His720Arg	missense_variant	9/11	5	NM_152405.5	ENSP00000379441.4
JMY	ENST00000412001.1	n.77-10514A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 8506 AN: 152110 Hom.: 543 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0449

GnomAD3 exomes AF: 0.0307 AC: 7647 AN: 249370 Hom.: 281 AF XY: 0.0293 AC XY: 3964 AN XY: 135286

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.0121

Gnomad EAS exome AF: 0.0670

Gnomad SAS exome AF: 0.0508

Gnomad FIN exome AF: 0.0143

Gnomad NFE exome AF: 0.0128

Gnomad OTH exome AF: 0.0269

GnomAD4 exome AF: 0.0212 AC: 30981 AN: 1461890 Hom.: 1001 Cov.: 33 AF XY: 0.0215 AC XY: 15668 AN XY: 727246

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0128

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0493

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0559 AC: 8517 AN: 152228 Hom.: 543 Cov.: 32 AF XY: 0.0557 AC XY: 4149 AN XY: 74444

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.0901

Gnomad4 SAS AF: 0.0467

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0501

Alfa AF: 0.0234 Hom.: 313

Bravo AF: 0.0607

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.0114 AC: 44

ESP6500AA AF: 0.141 AC: 567

ESP6500EA AF: 0.0128 AC: 108

ExAC AF: 0.0339 AC: 4104

Asia WGS AF: 0.0690 AC: 239 AN: 3478

EpiCase AF: 0.0134

EpiControl AF: 0.0152

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.5
DANN	Benign	0.54
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.15
Sift	Benign	0.18	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.011
ClinPred		0.0011	T
GERP RS		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.20

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: rs16876657; hg19: chr5-78610174;