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GeneBe

14-93721528-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_178013.4(PRIMA1):c.378C>T(p.Asp126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000085 ( 0 hom. )

Consequence

PRIMA1
NM_178013.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.958
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 14-93721528-G-A is Benign according to our data. Variant chr14-93721528-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 542929.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.958 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRIMA1NM_178013.4 linkuse as main transcriptc.378C>T p.Asp126= synonymous_variant 5/5 ENST00000393140.6
PRIMA1XM_011536456.3 linkuse as main transcriptc.378C>T p.Asp126= synonymous_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRIMA1ENST00000393140.6 linkuse as main transcriptc.378C>T p.Asp126= synonymous_variant 5/51 NM_178013.4 P1Q86XR5-1
PRIMA1ENST00000393143.5 linkuse as main transcriptc.378C>T p.Asp126= synonymous_variant 4/41 P1Q86XR5-1
PRIMA1ENST00000316227.3 linkuse as main transcriptc.*174C>T 3_prime_UTR_variant 5/51 Q86XR5-2
PRIMA1ENST00000477603.5 linkuse as main transcriptc.*174C>T 3_prime_UTR_variant, NMD_transcript_variant 6/61 Q86XR5-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000789
AC:
12
AN:
152010
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
16
AN:
250922
Hom.:
0
AF XY:
0.0000664
AC XY:
9
AN XY:
135636
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000849
AC:
124
AN:
1461220
Hom.:
0
Cov.:
32
AF XY:
0.0000825
AC XY:
60
AN XY:
726944
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000927
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000789
AC:
12
AN:
152010
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000725
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000859
Hom.:
0
Bravo
AF:
0.000121
EpiCase
AF:
0.000218
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Sleep-related hypermotor epilepsy Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 28, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
Cadd
Benign
5.9
Dann
Benign
0.50

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199535476; hg19: chr14-94187874; COSMIC: COSV60265951; API