chr11-35489359-T-G

Variant names:

• chr11-35489359-T-G
• rs10768140
• NM_001001991.3:c.379+2686A>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.379+2686A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,056 control chromosomes in the GnomAD database, including 26,299 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 0.54 (26299 hom., cov: 31)
• Consequence: PAMR1 NM_001001991.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAMR1	NM_001001991.3	c.379+2686A>C		intron_variant	Intron 3 of 10	ENST00000619888.5	NP_001001991.1
PAMR1	NM_015430.4	c.379+2686A>C		intron_variant	Intron 3 of 11		NP_056245.2
PAMR1	NM_001282675.2	c.259+2686A>C		intron_variant	Intron 5 of 12		NP_001269604.1
PAMR1	NM_001282676.2	c.379+2686A>C		intron_variant	Intron 3 of 8		NP_001269605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAMR1	ENST00000619888.5	c.379+2686A>C		intron_variant	Intron 3 of 10	1	NM_001001991.3	ENSP00000483703.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82636 AN: 151938 Hom.: 26293 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.544 AC: 82645 AN: 152056 Hom.: 26299 Cov.: 31 AF XY: 0.545 AC XY: 40481 AN XY: 74314

African (AFR) AF: 0.198 AC: 8223 AN: 41470

American (AMR) AF: 0.613 AC: 9358 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2449 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2177 AN: 5178

South Asian (SAS) AF: 0.552 AC: 2659 AN: 4820

European-Finnish (FIN) AF: 0.760 AC: 8045 AN: 10588

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47694 AN: 67940

Other (OTH) AF: 0.573 AC: 1212 AN: 2116

Alfa AF: 0.655 Hom.: 57088

Bravo AF: 0.520

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.60
PhyloP100		0.41
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: rs10768140; hg19: chr11-35510907;