chrX-31120136-T-C

Variant names:

• chrX-31120136-T-C
• rs7886658
• NM_004006.3:c.*1783A>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.*1783A>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 0.0252 in 111,003 control chromosomes in the GnomAD database, including 68 homozygotes. There are 859 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (68 hom., 859 hem., cov: 22)
  • Exomes 𝑓: 0.0033 (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: -0.385
• Publications: 0 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=-0.59).
• BP6: Variant X-31120136-T-C is Benign according to our data. Variant chrX-31120136-T-C is described in ClinVar as Benign. ClinVar VariationId is 368205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 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.*1783A>G		3_prime_UTR	Exon 79 of 79	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.*1783A>G		3_prime_UTR	Exon 79 of 79	NP_004000.1	P11532
	DMD	NM_000109.4		c.*1783A>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.*1783A>G		3_prime_UTR	Exon 79 of 79	ENSP00000354923.3	P11532-1
	DMD	ENST00000378723.7	TSL:1	c.*1697A>G		3_prime_UTR	Exon 17 of 17	ENSP00000367997.3	P11532-6
	DMD	ENST00000378677.6	TSL:5	c.*1783A>G		3_prime_UTR	Exon 79 of 79	ENSP00000367948.2	P11532-11

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 2782 AN: 110650 Hom.: 63 Cov.: 22

Gnomad AFR AF: 0.0609

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00669

Gnomad ASJ AF: 0.000384

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.00732

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000646

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00333 AC: 1 AN: 300 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128

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: 0.00338 AC: 1 AN: 296

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1

Other (OTH) AF: 0.00 AC: 0 AN: 3

GnomAD4 genome AF: 0.0252 AC: 2793 AN: 110703 Hom.: 68 Cov.: 22 AF XY: 0.0256 AC XY: 859 AN XY: 33555

African (AFR) AF: 0.0608 AC: 1866 AN: 30675

American (AMR) AF: 0.00668 AC: 70 AN: 10475

Ashkenazi Jewish (ASJ) AF: 0.000384 AC: 1 AN: 2601

East Asian (EAS) AF: 0.114 AC: 407 AN: 3560

South Asian (SAS) AF: 0.128 AC: 336 AN: 2632

European-Finnish (FIN) AF: 0.00732 AC: 42 AN: 5736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.000627 AC: 33 AN: 52613

Other (OTH) AF: 0.0251 AC: 38 AN: 1514

Alfa AF: 0.0129 Hom.: 152

Bravo AF: 0.0268

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	-0.59
CADD	Benign	1.4
DANN	Benign	0.68
PhyloP100		-0.39
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: rs7886658; hg19: chrX-31138253;