19-12792245-C-T

Variant names:

• chr19-12792245-C-T
• rs2229510
• NM_002229.3:c.474C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_002229.3(JUNB):​c.474C>T​(p.Ser158Ser) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JUNB NM_002229.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 11 publications found

Genes affected

JUNB (HGNC:6205): (JunB proto-oncogene, AP-1 transcription factor subunit) Enables sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor AP-1 complex. Biomarker of Hodgkin's lymphoma and anaplastic large cell lymphoma. [provided by Alliance of Genome Resources, Apr 2022]

HOOK2 (HGNC:19885): (hook microtubule tethering protein 2) Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment.[supplied by OMIM, Apr 2004]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=-0.099 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JUNB	NM_002229.3	c.474C>T	p.Ser158Ser	synonymous_variant	Exon 1 of 1	ENST00000302754.6	NP_002220.1
HOOK2	NM_001400043.1	c.-209+79G>A		intron_variant	Intron 1 of 21		NP_001386972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JUNB	ENST00000302754.6	c.474C>T	p.Ser158Ser	synonymous_variant	Exon 1 of 1	6	NM_002229.3	ENSP00000303315.4
HOOK2	ENST00000589765.1	n.42-18020G>A		intron_variant	Intron 3 of 3	5
HOOK2	ENST00000593143.5	n.259+79G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1358614 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 666538

African (AFR) AF: 0.00 AC: 0 AN: 30278

American (AMR) AF: 0.00 AC: 0 AN: 28678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22094

East Asian (EAS) AF: 0.00 AC: 0 AN: 35826

South Asian (SAS) AF: 0.00 AC: 0 AN: 75030

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058896

Other (OTH) AF: 0.00 AC: 0 AN: 56012

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 41

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.9
DANN	Benign	0.94
PhyloP100		-0.099
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2229510; hg19: chr19-12903059;