12-6913959-A-C

Variant names:

• chr12-6913959-A-C
• rs710415
• ENST00000323702.9:c.827A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001135217.2(LRRC23):​c.*93A>C variant causes a 3 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC23 NM_001135217.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910
• Publications: 48 publications found

Genes affected

LRRC23 (HGNC:19138): (leucine rich repeat containing 23) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENO2 (HGNC:3353): (enolase 2) This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme, a homodimer, is found in mature neurons and cells of neuronal origin. A switch from alpha enolase to gamma enolase occurs in neural tissue during development in rats and primates. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0629012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC23	NM_001135217.2	c.*93A>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000443597.7	NP_001128689.1
LRRC23	NM_006992.4	c.827A>C	p.Glu276Ala	missense_variant	Exon 7 of 7		NP_008923.1
LRRC23	NM_201650.3	c.*93A>C		3_prime_UTR_variant	Exon 8 of 8		NP_964013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC23	ENST00000443597.7	c.*93A>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001135217.2	ENSP00000390932.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461568 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727140

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.1
DANN	Uncertain	0.99
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.091
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.049
Sift	Benign	0.28	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.37		Gain of catalytic residue at H271 (P = 0.0244);
MVP		0.17
ClinPred		0.072	T
GERP RS		-0.78
PromoterAI		0.0037	Neutral
Mutation Taster		=99/1	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

dbSNP: rs710415; hg19: chr12-7023123;