NM_014982.3:c.762T>G

Variant names:

• chr14-70977099-T-G
• rs35702999
• NM_014982.3:c.762T>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014982.3(PCNX1):​c.762T>G​(p.Ser254Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,182 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0090 (10 hom., cov: 31)
  • Exomes 𝑓: 0.012 (148 hom.)
• Consequence: PCNX1 NM_014982.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.130
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 14-70977099-T-G is Benign according to our data. Variant chr14-70977099-T-G is described in ClinVar as Benign. ClinVar VariationId is 2644351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.13 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 gene

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.762T>G	p.Ser254Ser	synonymous	Exon 6 of 36	NP_055797.2	Q96RV3-1
	PCNX1	NM_001308160.2		c.762T>G	p.Ser254Ser	synonymous	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.762T>G	p.Ser254Ser	synonymous	Exon 6 of 36	ENSP00000304192.2	Q96RV3-1
	PCNX1	ENST00000439984.7	TSL:1	c.762T>G	p.Ser254Ser	synonymous	Exon 6 of 34	ENSP00000396617.3	Q96RV3-4
	PCNX1	ENST00000554879.5	TSL:1	n.1208T>G		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes AF: 0.00898 AC: 1367 AN: 152190 Hom.: 10 Cov.: 31

Gnomad AFR AF: 0.00198

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00655

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00981 AC: 2466 AN: 251438 AF XY: 0.0100

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00169

Gnomad FIN exome AF: 0.0254

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0122 AC: 17804 AN: 1461874 Hom.: 148 Cov.: 33 AF XY: 0.0119 AC XY: 8684 AN XY: 727240

African (AFR) AF: 0.00140 AC: 47 AN: 33480

American (AMR) AF: 0.00364 AC: 163 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00325 AC: 85 AN: 26136

East Asian (EAS) AF: 0.0141 AC: 561 AN: 39694

South Asian (SAS) AF: 0.00574 AC: 495 AN: 86258

European-Finnish (FIN) AF: 0.0256 AC: 1368 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0130 AC: 14411 AN: 1111998

Other (OTH) AF: 0.0111 AC: 670 AN: 60396

GnomAD4 genome AF: 0.00898 AC: 1367 AN: 152308 Hom.: 10 Cov.: 31 AF XY: 0.00954 AC XY: 710 AN XY: 74462

African (AFR) AF: 0.00197 AC: 82 AN: 41576

American (AMR) AF: 0.00392 AC: 60 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00656 AC: 34 AN: 5182

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4828

European-Finnish (FIN) AF: 0.0254 AC: 270 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0124 AC: 842 AN: 68024

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0104 Hom.: 4

Bravo AF: 0.00684

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.0121

EpiControl AF: 0.00948

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.9
DANN	Benign	0.77
PhyloP100		0.13
Mutation Taster		=100/0	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: rs35702999; hg19: chr14-71443816;