12-120710583-C-T

Variant names:

• chr12-120710583-C-T
• rs781389340
• NM_001080533.3:c.109C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080533.3(UNC119B):​c.109C>T​(p.Arg37Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000473 in 1,269,826 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: UNC119B NM_001080533.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

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]

ENSG00000294027 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28923255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080533.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC119B	NM_001080533.3	MANE Select	c.109C>T	p.Arg37Cys	missense	Exon 1 of 5	NP_001074002.1	A6NIH7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC119B	ENST00000344651.5	TSL:2 MANE Select	c.109C>T	p.Arg37Cys	missense	Exon 1 of 5	ENSP00000344942.4	A6NIH7
	UNC119B	ENST00000718082.1		c.109C>T	p.Arg37Cys	missense	Exon 1 of 4	ENSP00000520660.1	A0ABB0MV57
	UNC119B	ENST00000953441.1		c.109C>T	p.Arg37Cys	missense	Exon 1 of 3	ENSP00000623500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 49108 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000473 AC: 6 AN: 1269826 Hom.: 0 Cov.: 33 AF XY: 0.00000481 AC XY: 3 AN XY: 624150

African (AFR) AF: 0.00 AC: 0 AN: 25388

American (AMR) AF: 0.00 AC: 0 AN: 18694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20428

East Asian (EAS) AF: 0.00 AC: 0 AN: 27594

South Asian (SAS) AF: 0.0000154 AC: 1 AN: 64966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3736

European-Non Finnish (NFE) AF: 0.00000488 AC: 5 AN: 1025492

Other (OTH) AF: 0.00 AC: 0 AN: 52220

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000340 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.00039	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.060
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.81	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.97	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.99	D
Vest4		0.29
MutPred		0.40		Gain of catalytic residue at L38 (P = 0.023)
MVP		0.043
MPC		1.7
ClinPred		0.97	D
GERP RS		1.9
PromoterAI		0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.53
Mutation Taster		=77/23	polymorphism

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: rs781389340; hg19: chr12-121148386;