NM_012317.4:c.79A>C

Variant names:

• chrX-141176943-T-G
• NM_012317.4:c.79A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012317.4(LDOC1):​c.79A>C​(p.Met27Leu) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: LDOC1 NM_012317.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

Genes affected

LDOC1 (HGNC:6548): (LDOC1 regulator of NFKB signaling) The protein encoded by this gene contains a leucine zipper-like motif and a proline-rich region that shares marked similarity with an SH3-binding domain. The protein localizes to the nucleus and is down-regulated in some cancer cell lines. It is thought to regulate the transcriptional response mediated by the nuclear factor kappa B (NF-kappaB). The gene has been proposed as a tumor suppressor gene whose protein product may have an important role in the development and/or progression of some cancers. [provided by RefSeq, Jul 2008]

SPANXA2-OT1 (HGNC:31683): (SPANXA2 overlapping transcript 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09082034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012317.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDOC1	NM_012317.4	MANE Select	c.79A>C	p.Met27Leu	missense	Exon 1 of 1	NP_036449.1	O95751

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDOC1	ENST00000370526.5	TSL:6 MANE Select	c.79A>C	p.Met27Leu	missense	Exon 1 of 1	ENSP00000359557.2	O95751
	LDOC1	ENST00000460721.1	TSL:1	n.74A>C		non_coding_transcript_exon	Exon 1 of 2
	LDOC1	ENST00000670989.1		n.156A>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.20	N
PhyloP100		1.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.029
Sift	Benign	0.42	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.41		Gain of catalytic residue at M27 (P = 0.148)
MVP		0.17
MPC		1.3
ClinPred		0.095	T
GERP RS		2.4
PromoterAI		0.055	Neutral
Varity_R		0.11
gMVP		0.88
Mutation Taster		=96/4	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

hg19: chrX-140271128;