X-140784004-C-G

Variant names:

• chrX-140784004-C-G
• ENST00000625883.2:n.917C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_173139.1(LINC00632):​n.1174C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: LINC00632 NR_173139.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46

Genes affected

LINC00632 (HGNC:27865): (long intergenic non-protein coding RNA 632)

CDR1 (HGNC:1798): (cerebellar degeneration related 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05165142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00632	NR_173139.1	n.1174C>G		non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173140.2	n.1281C>G		non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	NR_173141.1	n.917C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00632	ENST00000625883.2	n.917C>G		non_coding_transcript_exon_variant	Exon 2 of 2	6
LINC00632	ENST00000648200.2	n.12023C>G		non_coding_transcript_exon_variant	Exon 5 of 5
LINC00632	ENST00000648347.1	n.713C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097928 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363326

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: 0.0000370

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.363G>C (p.K121N) alteration is located in exon 1 (coding exon 1) of the CDR1 gene. This alteration results from a G to C substitution at nucleotide position 363, causing the lysine (K) at amino acid position 121 to be replaced by an asparagine (N). 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	0.22
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.80
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.038
Sift	Benign	0.47	T
Sift4G	Benign	0.41	T
Polyphen		0.48	P
Vest4		0.079
MutPred		0.33		Loss of ubiquitination at K121 (P = 0.0092);
MVP		0.43
MPC		0.30
ClinPred		0.075	T
GERP RS		-1.2
Varity_R		0.058
gMVP		0.019

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: chrX-139866169;