16-11273546-C-A

Variant names:

• chr16-11273546-C-A
• rs963369373
• NM_021247.3:c.50G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021247.3(PRM3):​c.50G>T​(p.Ser17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S17N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRM3 NM_021247.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0530
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12263176).

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.50G>T	p.Ser17Ile	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.50G>T	p.Ser17Ile	missense	Exon 1 of 1	ENSP00000325638.2	Q9NNZ6
	RMI2	ENST00000572173.1	TSL:1	c.-515-21670C>A		intron	N/A	ENSP00000461206.1	Q96E14-2
	RMI2	ENST00000573910.1	TSL:3	n.160+23768C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152274 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458838 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 725894

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111378

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152274 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74394

African (AFR) AF: 0.0000241 AC: 1 AN: 41482

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.94
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.065	N
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.053
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.091
Sift	Benign	0.059	T
Sift4G	Benign	0.066	T
Vest4		0.25
MutPred		0.20		Loss of phosphorylation at S17 (P = 0.0146)
MVP		0.39
ClinPred		0.29	T
GERP RS		0.68
PromoterAI		-0.048	Neutral
gMVP		0.020

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: rs963369373; hg19: chr16-11367403;