NM_178013.4:c.99G>A

Variant names:

• chr14-93779306-C-T
• rs4900195
• NM_178013.4:c.99G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178013.4(PRIMA1):​c.99G>A​(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,544,294 control chromosomes in the GnomAD database, including 168,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.44 (14766 hom., cov: 29)
  • Exomes 𝑓: 0.46 (153542 hom.)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.05
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 14-93779306-C-T is Benign according to our data. Variant chr14-93779306-C-T is described in ClinVar as Benign. ClinVar VariationId is 586378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	NM_178013.4	MANE Select	c.99G>A	p.Thr33Thr	synonymous	Exon 3 of 5	NP_821092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRIMA1	ENST00000393140.6	TSL:1 MANE Select	c.99G>A	p.Thr33Thr	synonymous	Exon 3 of 5	ENSP00000376848.1
	PRIMA1	ENST00000393143.5	TSL:1	c.99G>A	p.Thr33Thr	synonymous	Exon 2 of 4	ENSP00000376851.1
	PRIMA1	ENST00000316227.3	TSL:1	c.99G>A	p.Thr33Thr	synonymous	Exon 2 of 5	ENSP00000320948.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66106 AN: 151184 Hom.: 14767 Cov.: 29

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.455

GnomAD2 exomes AF: 0.392 AC: 74717 AN: 190516 AF XY: 0.399

Gnomad AFR exome AF: 0.383

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.388

Gnomad EAS exome AF: 0.187

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.452

Gnomad OTH exome AF: 0.419

GnomAD4 exome AF: 0.463 AC: 645605 AN: 1392992 Hom.: 153542 Cov.: 34 AF XY: 0.461 AC XY: 318572 AN XY: 691422

African (AFR) AF: 0.391 AC: 11308 AN: 28896

American (AMR) AF: 0.282 AC: 9459 AN: 33558

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 9728 AN: 24318

East Asian (EAS) AF: 0.253 AC: 8806 AN: 34804

South Asian (SAS) AF: 0.352 AC: 26540 AN: 75442

European-Finnish (FIN) AF: 0.484 AC: 24499 AN: 50660

Middle Eastern (MID) AF: 0.403 AC: 2258 AN: 5598

European-Non Finnish (NFE) AF: 0.487 AC: 527073 AN: 1082138

Other (OTH) AF: 0.450 AC: 25934 AN: 57578

GnomAD4 genome AF: 0.437 AC: 66124 AN: 151302 Hom.: 14766 Cov.: 29 AF XY: 0.433 AC XY: 32037 AN XY: 73918

African (AFR) AF: 0.401 AC: 16478 AN: 41138

American (AMR) AF: 0.422 AC: 6409 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3464

East Asian (EAS) AF: 0.231 AC: 1179 AN: 5114

South Asian (SAS) AF: 0.355 AC: 1695 AN: 4780

European-Finnish (FIN) AF: 0.487 AC: 5095 AN: 10470

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32446 AN: 67844

Other (OTH) AF: 0.452 AC: 952 AN: 2106

Alfa AF: 0.436 Hom.: 11502

Bravo AF: 0.431

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Familial sleep-related hypermotor epilepsy (1)
-	-	1	PRIMA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.5
DANN	Benign	0.83
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs4900195; hg19: chr14-94245652; COSMIC: COSV60263382;