14-93779177-T-C

Variant names:

• chr14-93779177-T-C
• rs368397994
• NM_178013.4:c.228A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_178013.4(PRIMA1):​c.228A>G​(p.Pro76Pro) variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P76P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: PRIMA1 NM_178013.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.08445
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=1.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRIMA1	NM_178013.4	c.228A>G	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5	ENST00000393140.6	NP_821092.1
PRIMA1	XM_011536456.3	c.228A>G	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5		XP_011534758.1
PRIMA1	XM_047430966.1	c.228A>G	p.Pro76Pro	splice_region_variant, 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.228A>G	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 3 of 5	1	NM_178013.4	ENSP00000376848.1
PRIMA1	ENST00000393143.5	c.228A>G	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 2 of 4	1		ENSP00000376851.1
PRIMA1	ENST00000316227.3	c.228A>G	p.Pro76Pro	splice_region_variant, synonymous_variant	Exon 2 of 5	1		ENSP00000320948.3
PRIMA1	ENST00000477603.5	n.228A>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 6	1		ENSP00000434370.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00 AC: 0 AN: 127928 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.084
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.10		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: rs368397994; hg19: chr14-94245523;