chr14-93779306-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_178013.4(PRIMA1):​c.99G>T​(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 14-93779306-C-A is Benign according to our data. Variant chr14-93779306-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1130704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

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>T	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>T	p.Thr33Thr	synonymous	Exon 3 of 5	ENSP00000376848.1
	PRIMA1	ENST00000393143.5	TSL:1	c.99G>T	p.Thr33Thr	synonymous	Exon 2 of 4	ENSP00000376851.1
	PRIMA1	ENST00000316227.3	TSL:1	c.99G>T	p.Thr33Thr	synonymous	Exon 2 of 5	ENSP00000320948.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.15e-7 AC: 1 AN: 1398832 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 694298

African (AFR) AF: 0.00 AC: 0 AN: 29084

American (AMR) AF: 0.00 AC: 0 AN: 33876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24440

East Asian (EAS) AF: 0.00 AC: 0 AN: 34868

South Asian (SAS) AF: 0.00 AC: 0 AN: 76144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1086122

Other (OTH) AF: 0.00 AC: 0 AN: 57798

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 11502

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Familial sleep-related hypermotor epilepsy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.80
DANN	Benign	0.81
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;