rs35262993

chr16-11281185-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_002761.3(PRM1):c.54G>A(p.Gln18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,614,198 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (15 hom.)
• Consequence: PRM1 NM_002761.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

Genes affected

PRM1 (HGNC:9447): (protamine 1) Predicted to enable DNA binding activity. Predicted to be involved in DNA packaging. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RMI2 (HGNC:28349): (RecQ mediated genome instability 2) RMI2 is a component of the BLM (RECQL3; MIM 604610) complex, which plays a role in homologous recombination-dependent DNA repair and is essential for genome stability (Xu et al., 2008 [PubMed 18923082]).[supplied by OMIM, Nov 2008]

LOC105371082 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00213 (3115/1461860) while in subpopulation MID AF= 0.0218 (126/5768). AF 95% confidence interval is 0.0187. There are 15 homozygotes in gnomad4_exome. There are 1593 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRM1	NM_002761.3	c.54G>A	p.Gln18=	synonymous_variant	1/2	ENST00000312511.4
LOC105371082	XR_933070.4	n.178+31407C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRM1	ENST00000312511.4	c.54G>A	p.Gln18=	synonymous_variant	1/2	1	NM_002761.3	P1
RMI2	ENST00000572173.1	c.-515-14031C>T		intron_variant		1
RMI2	ENST00000573910.1	n.160+31407C>T		intron_variant, non_coding_transcript_variant		3
RMI2	ENST00000649869.1	n.152+31407C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00570 AC: 867 AN: 152220 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00311 AC: 782 AN: 251438 Hom.: 3 AF XY: 0.00280 AC XY: 381 AN XY: 135896

Gnomad AFR exome AF: 0.0169

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00287

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.00192

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00213 AC: 3115 AN: 1461860 Hom.: 15 Cov.: 34 AF XY: 0.00219 AC XY: 1593 AN XY: 727236

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.00282

Gnomad4 ASJ exome AF: 0.00696

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00293

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00374

GnomAD4 genome AF: 0.00569 AC: 867 AN: 152338 Hom.: 4 Cov.: 33 AF XY: 0.00513 AC XY: 382 AN XY: 74496

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00478 Hom.: 3

Bravo AF: 0.00666

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00327

EpiControl AF: 0.00243

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.12
Dann	Benign	0.70

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

Other links and lift over

dbSNP: rs35262993; hg19: chr16-11375042;