14-93779306-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_178013.4(PRIMA1):​c.99G>C​(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,550,266 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Benign.

• Frequency:
  • Genomes: 𝑓 0.00048 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00027 (2 hom.)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 14-93779306-C-G is Benign according to our data. Variant chr14-93779306-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 586379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMA1	NM_178013.4	c.99G>C	p.Thr33Thr	synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1
PRIMA1	XM_011536456.3	c.99G>C	p.Thr33Thr	synonymous_variant	Exon 3 of 5		XP_011534758.1
PRIMA1	XM_047430966.1	c.99G>C	p.Thr33Thr	synonymous_variant	Exon 3 of 5		XP_047286922.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000482 AC: 73 AN: 151320 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00356

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: 0.000206

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000341 AC: 65 AN: 190516 AF XY: 0.000351

Gnomad AFR exome AF: 0.0000885

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000269

Gnomad OTH exome AF: 0.000474

GnomAD4 exome AF: 0.000272 AC: 380 AN: 1398828 Hom.: 2 Cov.: 34 AF XY: 0.000278 AC XY: 193 AN XY: 694296

African (AFR) AF: 0.0000688 AC: 2 AN: 29084

American (AMR) AF: 0.00245 AC: 83 AN: 33876

Ashkenazi Jewish (ASJ) AF: 0.0000409 AC: 1 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: 0.000255 AC: 277 AN: 1086118

Other (OTH) AF: 0.000294 AC: 17 AN: 57798

GnomAD4 genome AF: 0.000482 AC: 73 AN: 151438 Hom.: 0 Cov.: 29 AF XY: 0.000473 AC XY: 35 AN XY: 73986

African (AFR) AF: 0.0000971 AC: 4 AN: 41196

American (AMR) AF: 0.00355 AC: 54 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67864

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00000869 Hom.: 11502

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 11, 2018

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial sleep-related hypermotor epilepsy Benign:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.57
DANN	Benign	0.72
PhyloP100		-1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs4900195; hg19: chr14-94245652;