NM_178013.4:c.420G>C

Variant names:

• chr14-93721486-C-G
• rs1887197
• NM_178013.4:c.420G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_178013.4(PRIMA1):​c.420G>C​(p.Ser140Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S140S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRIMA1 NM_178013.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 19 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-1.83 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.420G>C	p.Ser140Ser	synonymous	Exon 5 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.420G>C	p.Ser140Ser	synonymous	Exon 5 of 5	ENSP00000376848.1
	PRIMA1	ENST00000393143.5	TSL:1	c.420G>C	p.Ser140Ser	synonymous	Exon 4 of 4	ENSP00000376851.1
	PRIMA1	ENST00000477603.5	TSL:1	n.*216G>C		non_coding_transcript_exon	Exon 6 of 6	ENSP00000434370.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 88953

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.10
DANN	Benign	0.52
PhyloP100		-1.8

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

Other links and lift over

dbSNP: rs1887197; hg19: chr14-94187832;