rs4900195

Positions:

• chr14-93779306-C-A
• chr14-93779306-C-G
• chr14-93779306-C-T

Variant summary

Our verdict is Likely benign. Variant got -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 (★).

• 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

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 Likely_benign. Variant got -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 id is 1130704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIMA1	NM_178013.4	c.99G>T	p.Thr33Thr	synonymous_variant	3/5	ENST00000393140.6	NP_821092.1
PRIMA1	XM_011536456.3	c.99G>T	p.Thr33Thr	synonymous_variant	3/5		XP_011534758.1
PRIMA1	XM_047430966.1	c.99G>T	p.Thr33Thr	synonymous_variant	3/5		XP_047286922.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRIMA1	ENST00000393140.6	c.99G>T	p.Thr33Thr	synonymous_variant	3/5	1	NM_178013.4	ENSP00000376848.1
PRIMA1	ENST00000393143.5	c.99G>T	p.Thr33Thr	synonymous_variant	2/4	1		ENSP00000376851.1
PRIMA1	ENST00000316227.3	c.99G>T	p.Thr33Thr	synonymous_variant	2/5	1		ENSP00000320948.3
PRIMA1	ENST00000477603.5	n.99G>T		non_coding_transcript_exon_variant	3/6	1		ENSP00000434370.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sleep-related hypermotor epilepsy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 21, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.80
DANN	Benign	0.81
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

Publications

LitVar

Other links and lift over

dbSNP: rs4900195; hg19: chr14-94245652;