6-116592949-ATTTTT-ATT

Variant names:

• chr6-116592949-ATTT-A
• rs2243350
• NM_015952.4:c.611-18_611-16delTTT

Variant summary

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

The NM_015952.4(RWDD1):​c.611-18_611-16delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,294,562 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 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 2 publications found

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]

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	NM_015952.4	MANE Select	c.611-18_611-16delTTT		intron	N/A	NP_057036.2
	RWDD1	NM_001007464.3		c.323-18_323-16delTTT		intron	N/A	NP_001007465.1
	RWDD1	NM_016104.4		c.323-18_323-16delTTT		intron	N/A	NP_057188.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RWDD1	ENST00000466444.7	TSL:1 MANE Select	c.611-30_611-28delTTT		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-30_323-28delTTT		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141990 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000535 AC: 78 AN: 145910 AF XY: 0.000603

Gnomad AFR exome AF: 0.0000945

Gnomad AMR exome AF: 0.000618

Gnomad ASJ exome AF: 0.00108

Gnomad EAS exome AF: 0.000643

Gnomad FIN exome AF: 0.000733

Gnomad NFE exome AF: 0.000463

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000132 AC: 171 AN: 1294562 Hom.: 0 AF XY: 0.000147 AC XY: 95 AN XY: 646474

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

African (AFR) AF: 0.000104 AC: 3 AN: 28952

American (AMR) AF: 0.000310 AC: 11 AN: 35444

Ashkenazi Jewish (ASJ) AF: 0.000349 AC: 8 AN: 22936

East Asian (EAS) AF: 0.000165 AC: 6 AN: 36472

South Asian (SAS) AF: 0.000200 AC: 15 AN: 75034

European-Finnish (FIN) AF: 0.000520 AC: 23 AN: 44268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4802

European-Non Finnish (NFE) AF: 0.0000977 AC: 97 AN: 992896

Other (OTH) AF: 0.000149 AC: 8 AN: 53758

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 141990 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 68786

African (AFR) AF: 0.00 AC: 0 AN: 38740

American (AMR) AF: 0.00 AC: 0 AN: 14222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3342

East Asian (EAS) AF: 0.00 AC: 0 AN: 4872

South Asian (SAS) AF: 0.00 AC: 0 AN: 4440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8668

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64604

Other (OTH) AF: 0.00 AC: 0 AN: 1942

Alfa AF: 0.00102 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81

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: rs2243350; hg19: chr6-116914112;