6-167303969-C-G

Variant names:

• chr6-167303969-C-G
• rs145360877
• NM_018974.4:c.676C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018974.4(UNC93A):​c.676C>G​(p.Arg226Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: UNC93A NM_018974.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93A	NM_018974.4	c.676C>G	p.Arg226Gly	missense_variant	Exon 5 of 8	ENST00000230256.8	NP_061847.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93A	ENST00000230256.8	c.676C>G	p.Arg226Gly	missense_variant	Exon 5 of 8	1	NM_018974.4	ENSP00000230256.3
UNC93A	ENST00000366829.2	c.550C>G	p.Arg184Gly	missense_variant	Exon 4 of 7	1		ENSP00000355794.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249058 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.7
DANN	Benign	0.91
DEOGEN2	Benign	0.0052	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.19
Sift	Benign	0.063	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0	B;.
Vest4		0.12
MutPred		0.51		Loss of helix (P = 0.0444);.;
MVP		0.40
MPC		0.30
ClinPred		0.041	T
GERP RS		-2.7
Varity_R		0.059
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.34		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145360877; hg19: chr6-167717457;