NM_032968.5:c.12G>C

Variant names:

• chrX-91835516-G-C
• rs144734965
• NM_032968.5:c.12G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032968.5(PCDH11X):​c.12G>C​(p.Leu4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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: 21)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: PCDH11X NM_032968.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

Genes affected

PCDH11X (HGNC:8656): (protocadherin 11 X-linked) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein consists of an extracellular domain containing 7 cadherin repeats, a transmembrane domain and a cytoplasmic tail that differs from those of the classical cadherins. The gene is located in a major X/Y block of homology and its Y homolog, despite divergence leading to coding region changes, is the most closely related cadherin family member. The protein is thought to play a fundamental role in cell-cell recognition essential for the segmental development and function of the central nervous system. Disruption of this gene may be associated with developmental dyslexia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10063845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH11X	NM_032968.5	c.12G>C	p.Leu4Phe	missense_variant	Exon 5 of 11	ENST00000682573.1	NP_116750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH11X	ENST00000682573.1	c.12G>C	p.Leu4Phe	missense_variant	Exon 5 of 11		NM_032968.5	ENSP00000507225.1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098205 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363585

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	.;T;.;.;.;.
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;T;T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.65	N;N;N;N;N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N
REVEL	Benign	0.053
Sift	Benign	0.041	D;D;D;T;D;D
Sift4G	Benign	0.19	T;T;T;T;T;T
Polyphen		0.0070	B;B;B;B;B;B
Vest4		0.067
MutPred		0.48		Gain of glycosylation at S5 (P = 0.135);Gain of glycosylation at S5 (P = 0.135);Gain of glycosylation at S5 (P = 0.135);Gain of glycosylation at S5 (P = 0.135);Gain of glycosylation at S5 (P = 0.135);Gain of glycosylation at S5 (P = 0.135);
MVP		0.56
MPC		1.3
ClinPred		0.062	T
GERP RS		1.4
Varity_R		0.19
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs144734965; hg19: chrX-91090515;