NM_004006.3:c.*1447A>G

Variant names:

• chrX-31120472-T-C
• rs3361
• NM_004006.3:c.*1447A>G

Variant summary

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

The NM_004006.3(DMD):​c.*1447A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 110,946 control chromosomes in the GnomAD database, including 5,687 homozygotes. There are 10,870 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (5687 hom., 10870 hem., cov: 23)
  • Exomes 𝑓: 0.11 (0 hom. 0 hem.)
• Consequence: DMD NM_004006.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22
• Publications: 8 publications found

Genes affected

DMD (HGNC:2928): (dystrophin) This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene. [provided by RefSeq, Dec 2016]

DMD Gene-Disease associations (from GenCC):

• Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• dilated cardiomyopathy 3B

  Inheritance: XL Classification: DEFINITIVE Submitted by: Ambry Genetics
• Duchenne and Becker muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Duchenne muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• progressive muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
• symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297249 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-31120472-T-C is Benign according to our data. Variant chrX-31120472-T-C is described in ClinVar as Benign. ClinVar VariationId is 368213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004006.3. 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
	DMD	NM_004006.3	MANE Select	c.*1447A>G		3_prime_UTR	Exon 79 of 79	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.*1447A>G		3_prime_UTR	Exon 79 of 79	NP_004000.1	P11532
	DMD	NM_000109.4		c.*1447A>G		3_prime_UTR	Exon 79 of 79	NP_000100.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMD	ENST00000357033.9	TSL:1 MANE Select	c.*1447A>G		3_prime_UTR	Exon 79 of 79	ENSP00000354923.3	P11532-1
	DMD	ENST00000378723.7	TSL:1	c.*1361A>G		3_prime_UTR	Exon 17 of 17	ENSP00000367997.3	P11532-6
	DMD	ENST00000378677.6	TSL:5	c.*1447A>G		3_prime_UTR	Exon 79 of 79	ENSP00000367948.2	P11532-11

Frequencies

GnomAD3 genomes AF: 0.338 AC: 37518 AN: 110883 Hom.: 5681 Cov.: 23

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.254

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.312

GnomAD4 exome AF: 0.111 AC: 1 AN: 9 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.339 AC: 37573 AN: 110937 Hom.: 5687 Cov.: 23 AF XY: 0.327 AC XY: 10870 AN XY: 33245

African (AFR) AF: 0.601 AC: 18274 AN: 30408

American (AMR) AF: 0.247 AC: 2597 AN: 10508

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 473 AN: 2634

East Asian (EAS) AF: 0.263 AC: 922 AN: 3507

South Asian (SAS) AF: 0.224 AC: 594 AN: 2657

European-Finnish (FIN) AF: 0.238 AC: 1402 AN: 5889

Middle Eastern (MID) AF: 0.265 AC: 57 AN: 215

European-Non Finnish (NFE) AF: 0.238 AC: 12615 AN: 52930

Other (OTH) AF: 0.318 AC: 482 AN: 1518

Alfa AF: 0.266 Hom.: 21093

Bravo AF: 0.355

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated cardiomyopathy 3B (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		1.2
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: rs3361; hg19: chrX-31138589;