19-18280971-T-C

Position:

• chr19-18280971-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005354.6(JUND):​c.514A>G​(p.Thr172Ala) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: JUND NM_005354.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

Genes affected

JUND (HGNC:6206): (JunD proto-oncogene, AP-1 transcription factor subunit) The protein encoded by this intronless gene is a member of the JUN family, and a functional component of the AP1 transcription factor complex. This protein has been proposed to protect cells from p53-dependent senescence and apoptosis. Alternative translation initiation site usage results in the production of different isoforms (PMID:12105216). [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05821398).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JUND	NM_005354.6	c.514A>G	p.Thr172Ala	missense_variant	1/1	ENST00000252818.5	NP_005345.3
JUND	NM_001286968.2	c.385A>G	p.Thr129Ala	missense_variant	1/1		NP_001273897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JUND	ENST00000252818.5	c.514A>G	p.Thr172Ala	missense_variant	1/1		NM_005354.6	ENSP00000252818	P1
JUND	ENST00000600972.1			upstream_gene_variant		2		ENSP00000475153

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Jan 29, 2024

The c.514A>G (p.T172A) alteration is located in exon 1 (coding exon 1) of the JUND gene. This alteration results from a A to G substitution at nucleotide position 514, causing the threonine (T) at amino acid position 172 to be replaced by an alanine (A). 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	0.056
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.5
DANN	Benign	0.53
DEOGEN2	Benign	0.036	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.020
Sift	Benign	0.68	T
Sift4G	Benign	0.90	T
Polyphen		0.0	B
Vest4		0.046
MutPred		0.41		Loss of glycosylation at T172 (P = 0.0016);
MVP		0.32
ClinPred		0.086	T
GERP RS		-0.52
Varity_R		0.055
gMVP		0.37

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: rs1969935125; hg19: chr19-18391781;