14-70977710-C-T

Variant names:

• chr14-70977710-C-T
• rs139776513
• NM_014982.3:c.1373C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014982.3(PCNX1):​c.1373C>T​(p.Ala458Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000875 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00057 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: PCNX1 NM_014982.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.332
• Publications: 3 publications found

Genes affected

PCNX1 (HGNC:19740): (pecanex 1) This gene encodes an evolutionarily conserved transmembrane protein similar to the pecanex protein in Drosophila. The fly protein is a component of the Notch signaling pathway, which functions in several developmental processes. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036266744).
• BP6: Variant 14-70977710-C-T is Benign according to our data. Variant chr14-70977710-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2285840.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014982.3. 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
	PCNX1	NM_014982.3	MANE Select	c.1373C>T	p.Ala458Val	missense	Exon 6 of 36	NP_055797.2	Q96RV3-1
	PCNX1	NM_001308160.2		c.1373C>T	p.Ala458Val	missense	Exon 6 of 34	NP_001295089.1	Q96RV3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX1	ENST00000304743.7	TSL:1 MANE Select	c.1373C>T	p.Ala458Val	missense	Exon 6 of 36	ENSP00000304192.2	Q96RV3-1
	PCNX1	ENST00000439984.7	TSL:1	c.1373C>T	p.Ala458Val	missense	Exon 6 of 34	ENSP00000396617.3	Q96RV3-4
	PCNX1	ENST00000554879.5	TSL:1	n.1819C>T		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes AF: 0.000572 AC: 87 AN: 152046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.00103 AC: 258 AN: 251344 AF XY: 0.00100

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000231

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00226

Gnomad NFE exome AF: 0.00172

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000907 AC: 1326 AN: 1461872 Hom.: 1 Cov.: 33 AF XY: 0.000905 AC XY: 658 AN XY: 727232

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000201 AC: 9 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00236 AC: 126 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00103 AC: 1147 AN: 1111996

Other (OTH) AF: 0.000629 AC: 38 AN: 60396

GnomAD4 genome AF: 0.000572 AC: 87 AN: 152164 Hom.: 0 Cov.: 31 AF XY: 0.000592 AC XY: 44 AN XY: 74378

African (AFR) AF: 0.000169 AC: 7 AN: 41528

American (AMR) AF: 0.000131 AC: 2 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68006

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.000849 Hom.: 0

Bravo AF: 0.000472

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00124 AC: 151

EpiCase AF: 0.000927

EpiControl AF: 0.00136

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.073
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.083
DANN	Benign	0.63
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.33
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.0090
Sift	Benign	0.37	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.012
MVP		0.043
MPC		0.10
ClinPred		0.022	T
GERP RS		-5.3
Varity_R		0.012
gMVP		0.15
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs139776513; hg19: chr14-71444427; COSMIC: COSV53091084; COSMIC: COSV53091084;