16-11281212-G-T

Variant names:

• chr16-11281212-G-T
• rs772747794
• NM_002761.3:c.27C>A

Variant summary

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

The NM_002761.3(PRM1):​c.27C>A​(p.Ser9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRM1 NM_002761.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM1	NM_002761.3	MANE Select	c.27C>A	p.Ser9Arg	missense	Exon 1 of 2	NP_002752.1	P04553

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRM1	ENST00000312511.4	TSL:1 MANE Select	c.27C>A	p.Ser9Arg	missense	Exon 1 of 2	ENSP00000310515.3	P04553
	RMI2	ENST00000572173.1	TSL:1	c.-515-14004G>T		intron	N/A	ENSP00000461206.1	Q96E14-2
	RMI2	ENST00000573910.1	TSL:3	n.160+31434G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251356 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.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.53	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.29	T
PhyloP100		2.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.16
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.39		Loss of phosphorylation at S9 (P = 4e-04)
MVP		0.20
MPC		0.32
ClinPred		0.97	D
GERP RS		4.4
PromoterAI		-0.0012	Neutral
Varity_R		0.77
gMVP		0.0084

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: rs772747794; hg19: chr16-11375069;