rs6683173

Variant names:

• chr1-114688551-C-T
• rs6683173
• NM_000036.3:c.215+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-114688551-C-T
• chr1-114688551-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000036.3(AMPD1):​c.215+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00561 in 1,614,076 control chromosomes in the GnomAD database, including 445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (221 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (224 hom.)
• Consequence: AMPD1 NM_000036.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.90
• Publications: 1 publications found

Genes affected

AMPD1 (HGNC:468): (adenosine monophosphate deaminase 1) Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

AMPD1 Gene-Disease associations (from GenCC):

• myopathy due to myoadenylate deaminase deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• adenosine monophosphate deaminase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-114688551-C-T is Benign according to our data. Variant chr1-114688551-C-T is described in ClinVar as Benign. ClinVar VariationId is 92335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000036.3. 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
	AMPD1	NM_000036.3	MANE Select	c.215+10G>A		intron	N/A	NP_000027.3	P23109-1
	AMPD1	NM_001172626.2		c.203+10G>A		intron	N/A	NP_001166097.2	P23109-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMPD1	ENST00000520113.7	TSL:1 MANE Select	c.215+10G>A		intron	N/A	ENSP00000430075.3	P23109-1
	AMPD1	ENST00000369538.4	TSL:2	c.203+10G>A		intron	N/A	ENSP00000358551.4	P23109-2
	AMPD1	ENST00000637080.1	TSL:5	n.218+10G>A		intron	N/A	ENSP00000489753.1	A0A1B0GTL6

Frequencies

GnomAD3 genomes AF: 0.0290 AC: 4417 AN: 152120 Hom.: 220 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0177

GnomAD2 exomes AF: 0.00760 AC: 1910 AN: 251336 AF XY: 0.00558

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00316 AC: 4625 AN: 1461838 Hom.: 224 Cov.: 31 AF XY: 0.00273 AC XY: 1988 AN XY: 727218

African (AFR) AF: 0.109 AC: 3663 AN: 33476

American (AMR) AF: 0.00557 AC: 249 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39698

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.000222 AC: 247 AN: 1111980

Other (OTH) AF: 0.00649 AC: 392 AN: 60394

GnomAD4 genome AF: 0.0291 AC: 4428 AN: 152238 Hom.: 221 Cov.: 32 AF XY: 0.0290 AC XY: 2159 AN XY: 74456

African (AFR) AF: 0.101 AC: 4182 AN: 41524

American (AMR) AF: 0.0116 AC: 177 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68024

Other (OTH) AF: 0.0175 AC: 37 AN: 2112

Alfa AF: 0.0132 Hom.: 150

Bravo AF: 0.0330

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Muscle AMP deaminase deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.043
DANN	Benign	0.36
PhyloP100		-1.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6683173;

hg19: chr1-115231172;