11-35473893-C-G

Variant names:

• chr11-35473893-C-G
• rs1996369
• NM_001001991.3:c.494+737G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001991.3(PAMR1):​c.494+737G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,916 control chromosomes in the GnomAD database, including 7,692 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7692 hom., cov: 32)
• Consequence: PAMR1 NM_001001991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 2 publications found

Genes affected

PAMR1 (HGNC:24554): (peptidase domain containing associated with muscle regeneration 1) Predicted to enable calcium ion binding activity and serine-type endopeptidase activity. Predicted to be involved in proteolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001991.3. 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
	PAMR1	NM_001001991.3	MANE Select	c.494+737G>C		intron	N/A	NP_001001991.1
	PAMR1	NM_015430.4		c.494+737G>C		intron	N/A	NP_056245.2
	PAMR1	NM_001282675.2		c.374+737G>C		intron	N/A	NP_001269604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAMR1	ENST00000619888.5	TSL:1 MANE Select	c.494+737G>C		intron	N/A	ENSP00000483703.1
	PAMR1	ENST00000622144.4	TSL:1	c.494+737G>C		intron	N/A	ENSP00000482899.1
	PAMR1	ENST00000621476.4	TSL:2	c.374+737G>C		intron	N/A	ENSP00000480961.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47228 AN: 151798 Hom.: 7688 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47254 AN: 151916 Hom.: 7692 Cov.: 32 AF XY: 0.305 AC XY: 22644 AN XY: 74242

African (AFR) AF: 0.413 AC: 17096 AN: 41388

American (AMR) AF: 0.212 AC: 3240 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5174

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4812

European-Finnish (FIN) AF: 0.252 AC: 2653 AN: 10542

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19618 AN: 67934

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.168 Hom.: 312

Bravo AF: 0.311

Asia WGS AF: 0.270 AC: 938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.23
DANN	Benign	0.50
PhyloP100		-1.4
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: rs1996369; hg19: chr11-35495441;