rs1800268

Variant names:

• chrX-32468639-C-T
• rs1800268
• NM_004006.3:c.3021G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-32468639-C-T
• chrX-32468639-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_004006.3(DMD):​c.3021G>A​(p.Ser1007Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 1,209,308 control chromosomes in the GnomAD database, including 158 homozygotes. There are 6,864 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (10 hom., 359 hem., cov: 22)
  • Exomes 𝑓: 0.018 (148 hom. 6505 hem.)
• Consequence: DMD NM_004006.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.0460
• Publications: 4 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant X-32468639-C-T is Benign according to our data. Variant chrX-32468639-C-T is described in ClinVar as Benign. ClinVar VariationId is 94548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0121 (1354/111514) while in subpopulation NFE AF = 0.019 (1010/53048). AF 95% confidence interval is 0.0181. There are 10 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1354 XL,AD gene.

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.3021G>A	p.Ser1007Ser	synonymous	Exon 23 of 79	NP_003997.2	P11532-1
	DMD	NM_004009.3		c.3009G>A	p.Ser1003Ser	synonymous	Exon 23 of 79	NP_004000.1	P11532
	DMD	NM_000109.4		c.2997G>A	p.Ser999Ser	synonymous	Exon 23 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.3021G>A	p.Ser1007Ser	synonymous	Exon 23 of 79	ENSP00000354923.3	P11532-1
	DMD	ENST00000378677.6	TSL:5	c.3009G>A	p.Ser1003Ser	synonymous	Exon 23 of 79	ENSP00000367948.2	P11532-11
	DMD	ENST00000420596.5	TSL:5	c.94-103440G>A		intron	N/A	ENSP00000399897.1	Q14172

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1352 AN: 111459 Hom.: 10 Cov.: 22

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0172

Gnomad ASJ AF: 0.00227

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00936

Gnomad FIN AF: 0.00183

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0141

GnomAD2 exomes AF: 0.0122 AC: 2235 AN: 182498 AF XY: 0.0134

Gnomad AFR exome AF: 0.00236

Gnomad AMR exome AF: 0.00947

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00288

Gnomad NFE exome AF: 0.0201

Gnomad OTH exome AF: 0.0138

GnomAD4 exome AF: 0.0182 AC: 19962 AN: 1097794 Hom.: 148 Cov.: 30 AF XY: 0.0179 AC XY: 6505 AN XY: 363266

African (AFR) AF: 0.00284 AC: 75 AN: 26395

American (AMR) AF: 0.00975 AC: 343 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.00206 AC: 40 AN: 19377

East Asian (EAS) AF: 0.0000663 AC: 2 AN: 30176

South Asian (SAS) AF: 0.0109 AC: 589 AN: 54131

European-Finnish (FIN) AF: 0.00375 AC: 152 AN: 40505

Middle Eastern (MID) AF: 0.0133 AC: 55 AN: 4129

European-Non Finnish (NFE) AF: 0.0214 AC: 17998 AN: 841838

Other (OTH) AF: 0.0154 AC: 708 AN: 46070

GnomAD4 genome AF: 0.0121 AC: 1354 AN: 111514 Hom.: 10 Cov.: 22 AF XY: 0.0106 AC XY: 359 AN XY: 33732

African (AFR) AF: 0.00318 AC: 98 AN: 30800

American (AMR) AF: 0.0171 AC: 178 AN: 10384

Ashkenazi Jewish (ASJ) AF: 0.00227 AC: 6 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3549

South Asian (SAS) AF: 0.00939 AC: 25 AN: 2663

European-Finnish (FIN) AF: 0.00183 AC: 11 AN: 6009

Middle Eastern (MID) AF: 0.0233 AC: 5 AN: 215

European-Non Finnish (NFE) AF: 0.0190 AC: 1010 AN: 53048

Other (OTH) AF: 0.0139 AC: 21 AN: 1510

Alfa AF: 0.0140 Hom.: 109

Bravo AF: 0.0125

EpiCase AF: 0.0182

EpiControl AF: 0.0220

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	not provided (3)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Dilated cardiomyopathy 3B (1)
-	-	1	Duchenne muscular dystrophy (1)
-	-	1	Duchenne muscular dystrophy;C0878544:Cardiomyopathy;C0917713:Becker muscular dystrophy;na:Dystrophin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.63
DANN	Benign	0.59
PhyloP100		0.046
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: rs1800268; hg19: chrX-32486756;