chr16-11281137-C-A

Variant names:

• chr16-11281137-C-A
• rs35576928
• NM_002761.3:c.102G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002761.3(PRM1):​c.102G>T​(p.Arg34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 1,614,194 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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. R34K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0078 (16 hom., cov: 33)
  • Exomes 𝑓: 0.0083 (79 hom.)
• Consequence: PRM1 NM_002761.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.445
• Publications: 19 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059812963).
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

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.102G>T	p.Arg34Ser	missense	Exon 1 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.102G>T	p.Arg34Ser	missense	Exon 1 of 2	ENSP00000310515.3
	RMI2	ENST00000572173.1	TSL:1	c.-515-14079C>A		intron	N/A	ENSP00000461206.1
	RMI2	ENST00000573910.1	TSL:3	n.160+31359C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00777 AC: 1183 AN: 152218 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0366

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00875 AC: 2199 AN: 251444 AF XY: 0.00873

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.00124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0339

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00749

GnomAD4 exome AF: 0.00829 AC: 12114 AN: 1461858 Hom.: 79 Cov.: 34 AF XY: 0.00804 AC XY: 5849 AN XY: 727230

African (AFR) AF: 0.00114 AC: 38 AN: 33480

American (AMR) AF: 0.00141 AC: 63 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.0343 AC: 1832 AN: 53396

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00884 AC: 9831 AN: 1112002

Other (OTH) AF: 0.00560 AC: 338 AN: 60396

GnomAD4 genome AF: 0.00777 AC: 1183 AN: 152336 Hom.: 16 Cov.: 33 AF XY: 0.00879 AC XY: 655 AN XY: 74492

African (AFR) AF: 0.00190 AC: 79 AN: 41584

American (AMR) AF: 0.00124 AC: 19 AN: 15304

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.0366 AC: 389 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 682 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00766 Hom.: 10

Bravo AF: 0.00460

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00296 AC: 13

ESP6500EA AF: 0.0105 AC: 90

ExAC AF: 0.0101 AC: 1225

EpiCase AF: 0.00731

EpiControl AF: 0.00794

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.79
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.035	N
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.45
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.041
Sift4G	Uncertain	0.0030	D
Polyphen		0.99	D
Vest4		0.48
MutPred		0.39		Gain of phosphorylation at R34 (P = 0.0024)
MPC		0.32
ClinPred		0.061	T
GERP RS		-1.1
PromoterAI		-0.044	Neutral
Varity_R		0.69
gMVP		0.029
Mutation Taster		=100/0	polymorphism

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: rs35576928; hg19: chr16-11374994;