ENST00000604534.5:c.566+979A>C

Variant names:

• chr1-95231973-A-C
• rs6671200
• ENST00000604534.5:c.566+979A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000604534.5(TLCD4-RWDD3):​c.566+979A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 152,320 control chromosomes in the GnomAD database, including 61,955 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61955 hom., cov: 35)
• Consequence: TLCD4-RWDD3 ENST00000604534.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791
• Publications: 20 publications found

Genes affected

TLCD4-RWDD3 (HGNC:49388): (TLCD4-RWDD3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM56 (transmembrane protein 56) and RWDD3 (RWD domain containing 3) genes on chromosome 1. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product, but it contains a distinct C-terminus due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

RWDD3-DT (HGNC:55839): (RWDD3 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD4-RWDD3	NM_001199691.1	c.566+979A>C		intron_variant	Intron 7 of 7		NP_001186620.1
RWDD3-DT	NR_125948.1	n.283+1727T>G		intron_variant	Intron 1 of 4
RWDD3-DT	NR_125949.1	n.283+1727T>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD4-RWDD3	ENST00000604534.5	c.566+979A>C		intron_variant	Intron 7 of 7	2		ENSP00000475025.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 137092 AN: 152202 Hom.: 61911 Cov.: 35

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.918

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.914

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.901 AC: 137196 AN: 152320 Hom.: 61955 Cov.: 35 AF XY: 0.903 AC XY: 67269 AN XY: 74488

African (AFR) AF: 0.838 AC: 34837 AN: 41556

American (AMR) AF: 0.941 AC: 14410 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3110 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5194 AN: 5194

South Asian (SAS) AF: 0.984 AC: 4750 AN: 4828

European-Finnish (FIN) AF: 0.913 AC: 9687 AN: 10614

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62161 AN: 68032

Other (OTH) AF: 0.915 AC: 1933 AN: 2112

Alfa AF: 0.909 Hom.: 189139

Bravo AF: 0.899

Asia WGS AF: 0.982 AC: 3417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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: rs6671200; hg19: chr1-95697529;