12-120719977-A-G

Variant names:

• chr12-120719977-A-G
• rs375589147
• NM_001080533.3:c.701A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001080533.3(UNC119B):​c.701A>G​(p.Asp234Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UNC119B NM_001080533.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.701A>G	p.Asp234Gly	missense	Exon 5 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.701A>G	p.Asp234Gly	missense	Exon 5 of 5	ENSP00000344942.4	A6NIH7
	UNC119B	ENST00000718082.1		c.587A>G	p.Asp196Gly	missense	Exon 4 of 4	ENSP00000520660.1	A0ABB0MV57
	UNC119B	ENST00000953441.1		c.416A>G	p.Asp139Gly	missense	Exon 3 of 3	ENSP00000623500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461888 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.60
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.0045	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.60
Sift	Benign	0.23	T
Sift4G	Benign	0.23	T
Polyphen		0.59	P
Vest4		0.58
MVP		0.59
MPC		1.3
ClinPred		0.98	D
GERP RS		6.1
Varity_R		0.61
gMVP		0.64
Mutation Taster		=48/52	disease causing

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: rs375589147; hg19: chr12-121157780;