6-116592949-ATTTT-A

Variant names:

• chr6-116592949-ATTTT-A
• rs2243350
• NM_015952.4:c.611-19_611-16delTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015952.4(RWDD1):​c.611-19_611-16delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000462 in 1,298,736 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.810
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.611-19_611-16delTTTT		intron	N/A	NP_057036.2
	RWDD1	NM_001007464.3		c.323-19_323-16delTTTT		intron	N/A	NP_001007465.1
	RWDD1	NM_016104.4		c.323-19_323-16delTTTT		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_611-27delTTTT		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-30_323-27delTTTT		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000462 AC: 6 AN: 1298736 Hom.: 0 AF XY: 0.00000771 AC XY: 5 AN XY: 648522

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

African (AFR) AF: 0.00 AC: 0 AN: 29022

American (AMR) AF: 0.00 AC: 0 AN: 35548

Ashkenazi Jewish (ASJ) AF: 0.0000868 AC: 2 AN: 23040

East Asian (EAS) AF: 0.00 AC: 0 AN: 36622

South Asian (SAS) AF: 0.0000265 AC: 2 AN: 75416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 995926

Other (OTH) AF: 0.00 AC: 0 AN: 53882

⚠️ 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 Cov.: 29

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;