dbSNP rs6477419: DMRT3:c.455-98T>C (chr9-989943-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021240.4(DMRT3):c.455-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,480,712 control chromosomes in the GnomAD database, including 47,780 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5050 hom., cov: 32)

Exomes 𝑓: 0.25 ( 42730 hom. )

Consequence

DMRT3
NM_021240.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Publications

4 publications found

Variant links:

Genes affected

DMRT3 (HGNC:13909): (doublesex and mab-3 related transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in male sex differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult walking behavior; transmission of nerve impulse; and ventral spinal cord interneuron specification. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRT3 links:

ENSG00000294527 (HGNC:):

ENSG00000294527 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT3	NM_021240.4 link	c.455-98T>C		intron_variant	Intron 1 of 1	ENST00000190165.3	NP_067063.1	Q9NQL9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DMRT3	ENST00000190165.3 link	c.455-98T>C	intron_variant	Intron 1 of 1	1	NM_021240.4	ENSP00000190165.2	Q9NQL9
DMRT3	ENST00000417254.1 link	c.-55T>C	5_prime_UTR_variant	Exon 1 of 1	6		ENSP00000387472.1	Q5W0Z5
ENSG00000294527	ENST00000724117.1 link	n.422-3917A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37715

AN:

152004

Hom.:

5041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.249

AC:

331217

AN:

1328592

Hom.:

42730

Cov.:

AF XY:

0.248

AC XY:

162279

AN XY:

654590

show subpopulations

African (AFR)

AF:

0.227

AC:

6679

AN:

29384

American (AMR)

AF:

0.199

AC:

5931

AN:

29858

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

2388

AN:

20066

East Asian (EAS)

AF:

0.289

AC:

11172

AN:

38682

South Asian (SAS)

AF:

0.220

AC:

15139

AN:

68898

European-Finnish (FIN)

AF:

0.385

AC:

18990

AN:

49264

Middle Eastern (MID)

AF:

0.124

AC:

654

AN:

5282

European-Non Finnish (NFE)

AF:

0.250

AC:

257562

AN:

1032098

Other (OTH)

AF:

0.231

AC:

12702

AN:

55060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

12157

24314

36471

48628

60785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9024

18048

27072

36096

45120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37749

AN:

152120

Hom.:

5050

Cov.:

AF XY:

0.255

AC XY:

18995

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.240

AC:

9964

AN:

41484

American (AMR)

AF:

0.207

AC:

3162

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

400

AN:

3472

East Asian (EAS)

AF:

0.286

AC:

1479

AN:

5166

South Asian (SAS)

AF:

0.225

AC:

1084

AN:

4818

European-Finnish (FIN)

AF:

0.420

AC:

4438

AN:

10574

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16536

AN:

68000

Other (OTH)

AF:

0.188

AC:

397

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1447

2894

4342

5789

7236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.242

Hom.:

1755

Bravo

AF:

0.232

Asia WGS

AF:

0.247

AC:

861

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.0

(source)

DANN

Benign

0.62

PhyloP100

0.025

PromoterAI

-0.0020

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over