16-11281009-G-T

Variant names:

• chr16-11281009-G-T
• rs737008
• NM_002761.3:c.139C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002761.3(PRM1):​c.139C>A​(p.Arg47Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,613,064 control chromosomes in the GnomAD database, including 378,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29914 hom., cov: 31)
  • Exomes 𝑓: 0.68 (348445 hom.)
• Consequence: PRM1 NM_002761.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.628
• Publications: 43 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-11281009-G-T is Benign according to our data. Variant chr16-11281009-G-T is described in ClinVar as Benign. ClinVar VariationId is 1272307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.628 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002761.3. 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
	PRM1	NM_002761.3	MANE Select	c.139C>A	p.Arg47Arg	synonymous	Exon 2 of 2	NP_002752.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM1	ENST00000312511.4	TSL:1 MANE Select	c.139C>A	p.Arg47Arg	synonymous	Exon 2 of 2	ENSP00000310515.3
	RMI2	ENST00000572173.1	TSL:1	c.-515-14207G>T		intron	N/A	ENSP00000461206.1
	RMI2	ENST00000573910.1	TSL:3	n.160+31231G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93671 AN: 151888 Hom.: 29908 Cov.: 31

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.616

GnomAD2 exomes AF: 0.584 AC: 146850 AN: 251478 AF XY: 0.592

Gnomad AFR exome AF: 0.529

Gnomad AMR exome AF: 0.352

Gnomad ASJ exome AF: 0.542

Gnomad EAS exome AF: 0.311

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.709

Gnomad OTH exome AF: 0.617

GnomAD4 exome AF: 0.680 AC: 994247 AN: 1461058 Hom.: 348445 Cov.: 57 AF XY: 0.676 AC XY: 491431 AN XY: 726888

African (AFR) AF: 0.531 AC: 17765 AN: 33458

American (AMR) AF: 0.366 AC: 16373 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 14209 AN: 26134

East Asian (EAS) AF: 0.293 AC: 11630 AN: 39692

South Asian (SAS) AF: 0.506 AC: 43609 AN: 86244

European-Finnish (FIN) AF: 0.697 AC: 37210 AN: 53414

Middle Eastern (MID) AF: 0.531 AC: 3064 AN: 5766

European-Non Finnish (NFE) AF: 0.730 AC: 810797 AN: 1111266

Other (OTH) AF: 0.656 AC: 39590 AN: 60362

GnomAD4 genome AF: 0.616 AC: 93682 AN: 152006 Hom.: 29914 Cov.: 31 AF XY: 0.607 AC XY: 45099 AN XY: 74296

African (AFR) AF: 0.541 AC: 22406 AN: 41436

American (AMR) AF: 0.492 AC: 7519 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1909 AN: 3468

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5158

South Asian (SAS) AF: 0.493 AC: 2378 AN: 4824

European-Finnish (FIN) AF: 0.692 AC: 7307 AN: 10562

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48374 AN: 67976

Other (OTH) AF: 0.611 AC: 1287 AN: 2108

Alfa AF: 0.654 Hom.: 68960

Bravo AF: 0.595

Asia WGS AF: 0.423 AC: 1473 AN: 3478

EpiCase AF: 0.695

EpiControl AF: 0.683

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		0.63
PromoterAI		0.0067	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs737008; hg19: chr16-11374866; COSMIC: COSV54113282; COSMIC: COSV54113282;