NM_018974.4:c.92G>A

Variant names:

• chr6-167294521-G-A
• rs139202559
• NM_018974.4:c.92G>A

Variant summary

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

The NM_018974.4(UNC93A):​c.92G>A​(p.Ser31Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S31I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UNC93A NM_018974.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72
• 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: 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_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.92G>A	p.Ser31Asn	missense	Exon 2 of 8	NP_061847.2
	UNC93A	NM_001143947.2		c.92G>A	p.Ser31Asn	missense	Exon 2 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.92G>A	p.Ser31Asn	missense	Exon 2 of 8	ENSP00000230256.3	Q86WB7-1
	UNC93A	ENST00000366829.2	TSL:1	c.92G>A	p.Ser31Asn	missense	Exon 2 of 7	ENSP00000355794.2	Q86WB7-2
	UNC93A	ENST00000860147.1		c.92G>A	p.Ser31Asn	missense	Exon 3 of 9	ENSP00000530206.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461762 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727192

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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: 53352

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		8.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.84
MutPred		0.58		Gain of loop (P = 0.0166)
MVP		0.69
MPC		0.84
ClinPred		1.0	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.91
gMVP		0.74
Mutation Taster		=15/85	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: rs139202559; hg19: chr6-167708009;