NM_018974.4:c.329C>T

Variant names:

• chr6-167296091-C-T
• NM_018974.4:c.329C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018974.4(UNC93A):​c.329C>T​(p.Ala110Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: UNC93A NM_018974.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• Publications: 0 publications found

Genes affected

UNC93A (HGNC:12570): (unc-93 homolog A) Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018974.4. 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
	UNC93A	NM_018974.4	MANE Select	c.329C>T	p.Ala110Val	missense	Exon 3 of 8	NP_061847.2
	UNC93A	NM_001143947.2		c.329C>T	p.Ala110Val	missense	Exon 3 of 7	NP_001137419.1	Q86WB7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93A	ENST00000230256.8	TSL:1 MANE Select	c.329C>T	p.Ala110Val	missense	Exon 3 of 8	ENSP00000230256.3	Q86WB7-1
	UNC93A	ENST00000366829.2	TSL:1	c.329C>T	p.Ala110Val	missense	Exon 3 of 7	ENSP00000355794.2	Q86WB7-2
	UNC93A	ENST00000860147.1		c.329C>T	p.Ala110Val	missense	Exon 4 of 9	ENSP00000530206.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000889 AC: 13 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727242

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: 53416

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

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

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	0.62
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		6.9
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.84		Loss of helix (P = 0.1299)
MVP		0.51
MPC		0.79
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.70
gMVP		0.89
Mutation Taster		=54/46	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

hg19: chr6-167709579;