rs138681708

Variant names:

• chr11-35432617-A-G
• rs138681708
• NM_001001991.3:c.1902T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001001991.3(PAMR1):​c.1902T>C​(p.His634His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00648 in 1,614,086 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0067 (32 hom.)
• Consequence: PAMR1 NM_001001991.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-35432617-A-G is Benign according to our data. Variant chr11-35432617-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641723.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.002 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAMR1	NM_001001991.3	MANE Select	c.1902T>C	p.His634His	synonymous	Exon 11 of 11	NP_001001991.1	Q6UXH9-1
	PAMR1	NM_015430.4		c.1953T>C	p.His651His	synonymous	Exon 12 of 12	NP_056245.2	Q6UXH9-2
	PAMR1	NM_001282675.2		c.1782T>C	p.His594His	synonymous	Exon 13 of 13	NP_001269604.1	A0A087WXE9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAMR1	ENST00000619888.5	TSL:1 MANE Select	c.1902T>C	p.His634His	synonymous	Exon 11 of 11	ENSP00000483703.1	Q6UXH9-1
	PAMR1	ENST00000622144.4	TSL:1	c.1953T>C	p.His651His	synonymous	Exon 12 of 12	ENSP00000482899.1	Q6UXH9-2
	PAMR1	ENST00000953162.1		c.1923T>C	p.His641His	synonymous	Exon 11 of 11	ENSP00000623221.1

Frequencies

GnomAD3 genomes AF: 0.00474 AC: 722 AN: 152198 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00817

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00511 AC: 1281 AN: 250788 AF XY: 0.00500

Gnomad AFR exome AF: 0.000864

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00991

Gnomad NFE exome AF: 0.00819

Gnomad OTH exome AF: 0.00848

GnomAD4 exome AF: 0.00666 AC: 9740 AN: 1461770 Hom.: 32 Cov.: 32 AF XY: 0.00653 AC XY: 4746 AN XY: 727152

African (AFR) AF: 0.000956 AC: 32 AN: 33480

American (AMR) AF: 0.00105 AC: 47 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00283 AC: 74 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39698

South Asian (SAS) AF: 0.000499 AC: 43 AN: 86222

European-Finnish (FIN) AF: 0.0113 AC: 604 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00772 AC: 8589 AN: 1111932

Other (OTH) AF: 0.00571 AC: 345 AN: 60396

GnomAD4 genome AF: 0.00474 AC: 722 AN: 152316 Hom.: 3 Cov.: 33 AF XY: 0.00450 AC XY: 335 AN XY: 74476

African (AFR) AF: 0.00111 AC: 46 AN: 41584

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00763 AC: 81 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00817 AC: 556 AN: 68014

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00679 Hom.: 2

Bravo AF: 0.00401

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00682

EpiControl AF: 0.00605

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.33
DANN	Benign	0.58
PhyloP100		0.0020
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: rs138681708; hg19: chr11-35454165;