14-93721486-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178013.4(PRIMA1):c.420G>A(p.Ser140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,612,388 control chromosomes in the GnomAD database, including 323,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26673 hom., cov: 31)
  • Exomes 𝑓: 0.63 (296338 hom.)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83

Genes affected

PRIMA1 (HGNC:18319): (proline rich membrane anchor 1) The product of this gene functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 14-93721486-C-T is Benign according to our data. Variant chr14-93721486-C-T is described in ClinVar as [Benign]. Clinvar id is 586377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.83 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRIMA1	NM_178013.4	c.420G>A	p.Ser140=	synonymous_variant	5/5	ENST00000393140.6
PRIMA1	XM_011536456.3	c.420G>A	p.Ser140=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRIMA1	ENST00000393140.6	c.420G>A	p.Ser140=	synonymous_variant	5/5	1	NM_178013.4	P1
PRIMA1	ENST00000393143.5	c.420G>A	p.Ser140=	synonymous_variant	4/4	1		P1
PRIMA1	ENST00000316227.3	c.*216G>A		3_prime_UTR_variant	5/5	1
PRIMA1	ENST00000477603.5	c.*216G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88386 AN: 151830 Hom.: 26667 Cov.: 31

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.610

GnomAD3 exomes AF: 0.607 AC: 152360 AN: 251012 Hom.: 47664 AF XY: 0.610 AC XY: 82765 AN XY: 135652

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.728

Gnomad EAS exome AF: 0.328

Gnomad SAS exome AF: 0.553

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.658

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.633 AC: 924802 AN: 1460440 Hom.: 296338 Cov.: 41 AF XY: 0.632 AC XY: 459312 AN XY: 726606

Gnomad4 AFR exome AF: 0.419

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.725

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.582 AC: 88431 AN: 151948 Hom.: 26673 Cov.: 31 AF XY: 0.583 AC XY: 43262 AN XY: 74250

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.547

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.603

Alfa AF: 0.648 Hom.: 57678

Bravo AF: 0.577

Asia WGS AF: 0.445 AC: 1555 AN: 3478

EpiCase AF: 0.666

EpiControl AF: 0.666

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Sleep-related hypermotor epilepsy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.13
Dann	Benign	0.61

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: rs1887197; hg19: chr14-94187832; COSMIC: COSV60262844;