16-11273338-G-C

Variant names:

• chr16-11273338-G-C
• rs35598356
• NM_021247.3:c.258C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021247.3(PRM3):​c.258C>G​(p.His86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,544,908 control chromosomes in the GnomAD database, including 27,037 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2075 hom., cov: 34)
  • Exomes 𝑓: 0.18 (24962 hom.)
• Consequence: PRM3 NM_021247.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.22
• Publications: 13 publications found

Genes affected

PRM3 (HGNC:13732): (protamine 3) Predicted to enable DNA binding activity. Predicted to be involved in flagellated sperm motility. Predicted to be located in nucleus. Predicted to be part of nucleosome. Predicted to be active in cytoplasm. [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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003490448).
• BP6: Variant 16-11273338-G-C is Benign according to our data. Variant chr16-11273338-G-C is described in ClinVar as Benign. ClinVar VariationId is 1231734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021247.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM3	NM_021247.3	MANE Select	c.258C>G	p.His86Gln	missense	Exon 1 of 1	NP_067070.2	Q9NNZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM3	ENST00000327157.4	TSL:6 MANE Select	c.258C>G	p.His86Gln	missense	Exon 1 of 1	ENSP00000325638.2	Q9NNZ6
	RMI2	ENST00000572173.1	TSL:1	c.-515-21878G>C		intron	N/A	ENSP00000461206.1	Q96E14-2
	RMI2	ENST00000573910.1	TSL:3	n.160+23560G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22159 AN: 152188 Hom.: 2078 Cov.: 34

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.0417

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.158 AC: 23291 AN: 147568 AF XY: 0.159

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.0260

Gnomad FIN exome AF: 0.204

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.183

GnomAD4 exome AF: 0.184 AC: 256896 AN: 1392602 Hom.: 24962 Cov.: 44 AF XY: 0.185 AC XY: 126855 AN XY: 687170

African (AFR) AF: 0.0338 AC: 1069 AN: 31596

American (AMR) AF: 0.129 AC: 4600 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 5029 AN: 25176

East Asian (EAS) AF: 0.0489 AC: 1749 AN: 35736

South Asian (SAS) AF: 0.137 AC: 10860 AN: 79226

European-Finnish (FIN) AF: 0.203 AC: 8645 AN: 42628

Middle Eastern (MID) AF: 0.201 AC: 1140 AN: 5680

European-Non Finnish (NFE) AF: 0.198 AC: 213453 AN: 1078904

Other (OTH) AF: 0.179 AC: 10351 AN: 57956

GnomAD4 genome AF: 0.145 AC: 22143 AN: 152306 Hom.: 2075 Cov.: 34 AF XY: 0.145 AC XY: 10769 AN XY: 74472

African (AFR) AF: 0.0385 AC: 1600 AN: 41572

American (AMR) AF: 0.150 AC: 2295 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3470

East Asian (EAS) AF: 0.0416 AC: 216 AN: 5192

South Asian (SAS) AF: 0.124 AC: 598 AN: 4828

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10608

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13998 AN: 68010

Other (OTH) AF: 0.172 AC: 364 AN: 2114

Alfa AF: 0.155 Hom.: 732

Bravo AF: 0.136

TwinsUK AF: 0.186 AC: 688

ALSPAC AF: 0.182 AC: 700

ESP6500AA AF: 0.0347 AC: 136

ESP6500EA AF: 0.180 AC: 1370

ExAC AF: 0.0853 AC: 4530

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0020
DANN	Benign	0.42
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0052	N
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.1	T
PhyloP100		-3.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.053
Sift	Benign	0.66	T
Sift4G	Benign	0.27	T
Vest4		0.014
MutPred		0.12		Gain of helix (P = 0.132)
ClinPred		0.013	T
GERP RS		-9.6
PromoterAI		-0.0029	Neutral
gMVP		0.0044
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: rs35598356; hg19: chr16-11367195; COSMIC: COSV54113937; COSMIC: COSV54113937;