Genetic Variant DMRTB1:p.Arg96Cys (chr1-53459739-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_033067.3(DMRTB1):c.286C>T(p.Arg96Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,355,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

DMRTB1
NM_033067.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.980

Publications

1 publications found

Variant links:

Genes affected

DMRTB1 (HGNC:13913): (DMRT like family B with proline rich C-terminal 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DMRTB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004362434).

BP6

Variant 1-53459739-C-T is Benign according to our data. Variant chr1-53459739-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2389261.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033067.3. 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
	DMRTB1	NM_033067.3	MANE Select	c.286C>T	p.Arg96Cys	missense	Exon 1 of 4	NP_149056.1	Q96MA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTB1	ENST00000371445.3	TSL:1 MANE Select	c.286C>T	p.Arg96Cys	missense	Exon 1 of 4	ENSP00000360500.3	Q96MA1
	DMRTB1	ENST00000463126.1	TSL:5	n.-237C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.000146

AC:

AN:

151058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000623

AC:

AN:

16062

AF XY:

0.000102

show subpopulations

Gnomad AFR exome

AF:

0.00980

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000183

AC:

AN:

1203854

Hom.:

Cov.:

AF XY:

0.0000255

AC XY:

AN XY:

587412

show subpopulations

African (AFR)

AF:

0.000535

AC:

AN:

22416

American (AMR)

AF:

0.00

AC:

AN:

9446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15578

East Asian (EAS)

AF:

0.00

AC:

AN:

24326

South Asian (SAS)

AF:

0.00

AC:

AN:

54250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3270

European-Non Finnish (NFE)

AF:

0.00000910

AC:

AN:

989532

Other (OTH)

AF:

0.0000208

AC:

AN:

48084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000152

AC:

AN:

151166

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

73886

show subpopulations

African (AFR)

AF:

0.000483

AC:

AN:

41416

American (AMR)

AF:

0.0000658

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67642

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000712

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.0000684

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

-0.98

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.38

REVEL

Benign

0.023

Sift

Benign

0.31

Sift4G

Benign

0.085

Polyphen

0.0070

Vest4

0.044

MutPred

0.20

Loss of methylation at R96 (P = 0.0426)

MVP

0.043

MPC

0.62

ClinPred

0.023

GERP RS

-6.4

PromoterAI

-0.080

Neutral

(source)

Varity_R

0.095

gMVP

0.15

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over