6-167305925-C-G

Position:

• chr6-167305925-C-G

Variant summary

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

The NM_018974.4(UNC93A):​c.851C>G​(p.Thr284Ser) variant causes a missense change. 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNC93A NM_018974.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

Genes affected

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

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=0.4158059).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC93A	NM_018974.4	c.851C>G	p.Thr284Ser	missense_variant	6/8	ENST00000230256.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93A	ENST00000230256.8	c.851C>G	p.Thr284Ser	missense_variant	6/8	1	NM_018974.4	P1
UNC93A	ENST00000366829.2	c.725C>G	p.Thr242Ser	missense_variant	5/7	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.851C>G (p.T284S) alteration is located in exon 6 (coding exon 6) of the UNC93A gene. This alteration results from a C to G substitution at nucleotide position 851, causing the threonine (T) at amino acid position 284 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.093
Sift	Benign	0.38	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.13	B;.
Vest4		0.52
MutPred		0.51		Gain of disorder (P = 0.0941);.;
MVP		0.014
MPC		0.26
ClinPred		0.95	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.30

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: chr6-167719413;