Genetic Variant RWDD1:c.611-17_611-16dupTT (chr6-116592949-A-ATT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015952.4(RWDD1):c.611-17_611-16dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,437,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

RWDD1
NM_015952.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0680

Publications

2 publications found

Variant links:

Genes affected

RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

RWDD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015952.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RWDD1	NM_015952.4	MANE Select	c.611-17_611-16dupTT	intron	N/A	NP_057036.2	Q9H446-1
RWDD1	NM_001007464.3		c.323-17_323-16dupTT	intron	N/A	NP_001007465.1	Q9H446-2
RWDD1	NM_016104.4		c.323-17_323-16dupTT	intron	N/A	NP_057188.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-31_611-30insTT		intron	N/A	ENSP00000420357.2	Q9H446-1
	RWDD1	ENST00000487832.6	TSL:1	c.323-31_323-30insTT		intron	N/A	ENSP00000428778.1	Q9H446-2

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

111

AN:

142010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000450

Gnomad FIN

AF:

0.000115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000139

Gnomad OTH

AF:

0.000515

GnomAD2 exomes

AF:

0.00299

AC:

436

AN:

145910

AF XY:

0.00280

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.00664

Gnomad ASJ exome

AF:

0.00234

Gnomad EAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.00220

Gnomad NFE exome

AF:

0.00232

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00132

AC:

1708

AN:

1295458

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

844

AN XY:

646878

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00463

AC:

134

AN:

28928

American (AMR)

AF:

0.00551

AC:

195

AN:

35400

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

22974

East Asian (EAS)

AF:

0.000493

AC:

AN:

36536

South Asian (SAS)

AF:

0.00157

AC:

118

AN:

75202

European-Finnish (FIN)

AF:

0.00146

AC:

AN:

44376

Middle Eastern (MID)

AF:

0.000833

AC:

AN:

4802

European-Non Finnish (NFE)

AF:

0.00107

AC:

1063

AN:

993454

Other (OTH)

AF:

0.00138

AC:

AN:

53786

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.274

Heterozygous variant carriers

175

351

526

702

877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

126

168

210

<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:

0.000810

AC:

115

AN:

142058

Hom.:

Cov.:

AF XY:

0.000741

AC XY:

AN XY:

68862

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

38832

American (AMR)

AF:

0.000281

AC:

AN:

14240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3342

East Asian (EAS)

AF:

0.00

AC:

AN:

4856

South Asian (SAS)

AF:

0.000452

AC:

AN:

4420

European-Finnish (FIN)

AF:

0.000115

AC:

AN:

8678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000139

AC:

AN:

64598

Other (OTH)

AF:

0.000512

AC:

AN:

1952

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00120

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.068

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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6-116592949-ATTTTT-ATTTTTTT

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