NM_001001991.3:c.1721C>T

Variant names:

• chr11-35432798-G-A
• rs773899087
• NM_001001991.3:c.1721C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001001991.3(PAMR1):​c.1721C>T​(p.Thr574Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,457,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: PAMR1 NM_001001991.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2914071).

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.1721C>T	p.Thr574Ile	missense	Exon 11 of 11	NP_001001991.1	Q6UXH9-1
	PAMR1	NM_015430.4		c.1772C>T	p.Thr591Ile	missense	Exon 12 of 12	NP_056245.2	Q6UXH9-2
	PAMR1	NM_001282675.2		c.1601C>T	p.Thr534Ile	missense	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.1721C>T	p.Thr574Ile	missense	Exon 11 of 11	ENSP00000483703.1	Q6UXH9-1
	PAMR1	ENST00000622144.4	TSL:1	c.1772C>T	p.Thr591Ile	missense	Exon 12 of 12	ENSP00000482899.1	Q6UXH9-2
	PAMR1	ENST00000953162.1		c.1742C>T	p.Thr581Ile	missense	Exon 11 of 11	ENSP00000623221.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000202 AC: 5 AN: 247316 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1457100 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724956

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.51	D
MutationAssessor	Benign	1.9	M
PhyloP100		2.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.45
Sift4G	Uncertain	0.031	D
Polyphen		0.045	B
Vest4		0.28
MutPred		0.39		Loss of sheet (P = 0.0817)
MVP		0.46
ClinPred		0.30	T
GERP RS		3.7
Varity_R		0.54
gMVP		0.49
Mutation Taster		=87/13	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: rs773899087; hg19: chr11-35454346;