6-116592949-ATTTTT-ATTTT

Variant names:

• chr6-116592949-AT-A
• rs2243350
• NM_015952.4:c.611-16delT

Variant summary

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

The NM_015952.4(RWDD1):​c.611-16delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 141,680 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0046 (1 hom., cov: 29)
  • Exomes 𝑓: 0.26 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RWDD1 NM_015952.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• 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.611-16delT		intron	N/A	NP_057036.2
	RWDD1	NM_001007464.3		c.323-16delT		intron	N/A	NP_001007465.1
	RWDD1	NM_016104.4		c.323-16delT		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.611-30delT		intron	N/A	ENSP00000420357.2
	RWDD1	ENST00000487832.6	TSL:1	c.323-30delT		intron	N/A	ENSP00000428778.1

Frequencies

GnomAD3 genomes AF: 0.00447 AC: 633 AN: 141636 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00269

Gnomad EAS AF: 0.00350

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00516

GnomAD2 exomes AF: 0.346 AC: 50424 AN: 145910 AF XY: 0.350

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.257

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.357

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.263 AC: 274497 AN: 1041750 Hom.: 0 Cov.: 0 AF XY: 0.268 AC XY: 139459 AN XY: 521206

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

African (AFR) AF: 0.227 AC: 5550 AN: 24396

American (AMR) AF: 0.210 AC: 6791 AN: 32394

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 5427 AN: 19582

East Asian (EAS) AF: 0.342 AC: 10168 AN: 29696

South Asian (SAS) AF: 0.290 AC: 18342 AN: 63258

European-Finnish (FIN) AF: 0.291 AC: 11126 AN: 38272

Middle Eastern (MID) AF: 0.272 AC: 1091 AN: 4018

European-Non Finnish (NFE) AF: 0.260 AC: 204211 AN: 786422

Other (OTH) AF: 0.270 AC: 11791 AN: 43712

⚠️ 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 AF: 0.00460 AC: 652 AN: 141680 Hom.: 1 Cov.: 29 AF XY: 0.00527 AC XY: 362 AN XY: 68640

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

African (AFR) AF: 0.00384 AC: 149 AN: 38794

American (AMR) AF: 0.00274 AC: 39 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.00269 AC: 9 AN: 3340

East Asian (EAS) AF: 0.00351 AC: 17 AN: 4848

South Asian (SAS) AF: 0.00136 AC: 6 AN: 4418

European-Finnish (FIN) AF: 0.0201 AC: 172 AN: 8568

Middle Eastern (MID) AF: 0.00362 AC: 1 AN: 276

European-Non Finnish (NFE) AF: 0.00385 AC: 248 AN: 64416

Other (OTH) AF: 0.00565 AC: 11 AN: 1948

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0873 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.068
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV63972127; COSMIC: COSV63972127;