NM_018974.4:c.334T>A

Variant names:

• chr6-167296096-T-A
• NM_018974.4:c.334T>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_018974.4(UNC93A):​c.334T>A​(p.Cys112Ser) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNC93A NM_018974.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69
• 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_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35646003).
• BP6: Variant 6-167296096-T-A is Benign according to our data. Variant chr6-167296096-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3466185.Status of the report is criteria_provided_single_submitter, 1 stars.

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.334T>A	p.Cys112Ser	missense	Exon 3 of 8	NP_061847.2
	UNC93A	NM_001143947.2		c.334T>A	p.Cys112Ser	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.334T>A	p.Cys112Ser	missense	Exon 3 of 8	ENSP00000230256.3	Q86WB7-1
	UNC93A	ENST00000366829.2	TSL:1	c.334T>A	p.Cys112Ser	missense	Exon 3 of 7	ENSP00000355794.2	Q86WB7-2
	UNC93A	ENST00000860147.1		c.334T>A	p.Cys112Ser	missense	Exon 4 of 9	ENSP00000530206.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.2
DANN	Benign	0.36
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.014	B
Vest4		0.21
MutPred		0.62		Gain of glycosylation at C112 (P = 0.0241)
MVP		0.085
MPC		0.31
ClinPred		0.21	T
GERP RS		-4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.77
Mutation Taster		=84/16	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: chr6-167709584;