chr6-167296096-T-A

Position:

• chr6-167296096-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

Genes affected

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

UNC93A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35646003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC93A	NM_018974.4	c.334T>A	p.Cys112Ser	missense_variant	3/8	ENST00000230256.8	NP_061847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93A	ENST00000230256.8	c.334T>A	p.Cys112Ser	missense_variant	3/8	1	NM_018974.4	ENSP00000230256.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.5	D;D;D
REVEL	Benign	0.17
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.014	.;B;.
Vest4		0.21, 0.27
MutPred		0.62		Gain of glycosylation at C112 (P = 0.0241);Gain of glycosylation at C112 (P = 0.0241);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-167709584;