rs1249355657

Variant names:

• chr12-120710647-C-A
• rs1249355657
• NM_001080533.3:c.173C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-120710647-C-A
• chr12-120710647-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080533.3(UNC119B):​c.173C>A​(p.Thr58Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T58M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UNC119B NM_001080533.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.55

Genes affected

UNC119B (HGNC:16488): (unc-119 lipid binding chaperone B) Enables lipid binding activity. Involved in cilium assembly and lipoprotein transport. Located in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903036 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3173805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC119B	NM_001080533.3	c.173C>A	p.Thr58Lys	missense_variant	Exon 1 of 5	ENST00000344651.5	NP_001074002.1
LOC124903036	XR_007063491.1	n.-141G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC119B	ENST00000344651.5	c.173C>A	p.Thr58Lys	missense_variant	Exon 1 of 5	2	NM_001080533.3	ENSP00000344942.4
UNC119B	ENST00000539658.1	n.131C>A		non_coding_transcript_exon_variant	Exon 1 of 4	5		ENSP00000520658.1
UNC119B	ENST00000618898.1	n.190C>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1296448 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 639168

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.66	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.015	D
Sift4G	Benign	0.16	T
Polyphen		0.67	P
Vest4		0.35
MutPred		0.40		Gain of ubiquitination at T58 (P = 0.0094);
MVP		0.043
MPC		0.87
ClinPred		0.98	D
GERP RS		1.4
Varity_R		0.23
gMVP		0.72

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: rs1249355657; hg19: chr12-121148450;