Genetic Variant DRC4:p.Thr350Thr (chr16-90040338-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001481.3(DRC4):c.1050C>A(p.Thr350Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T350T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DRC4
NM_001481.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.60

Publications

6 publications found

Variant links:

Genes affected

DRC4 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

DRC4 links:

URAHP (HGNC:):

URAHP links:

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

URAHP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-5.6 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001481.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DRC4	NM_001481.3	MANE Select	c.1050C>A	p.Thr350Thr	synonymous	Exon 9 of 11	NP_001472.1	O95995-1
DRC4	NM_001286209.2		c.975C>A	p.Thr325Thr	synonymous	Exon 9 of 11	NP_001273138.1	O95995-2
DRC4	NM_001286205.2		c.801C>A	p.Thr267Thr	synonymous	Exon 9 of 11	NP_001273134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1050C>A	p.Thr350Thr	synonymous	Exon 9 of 11	ENSP00000268699.4	O95995-1
URAHP	ENST00000409873.5	TSL:1	n.772G>T		non_coding_transcript_exon	Exon 5 of 5
GAS8	ENST00000566266.5	TSL:1	n.*1010C>A		non_coding_transcript_exon	Exon 8 of 10	ENSP00000454343.1	H3BME0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719606

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.00

AC:

AN:

43142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25854

East Asian (EAS)

AF:

0.00

AC:

AN:

38934

South Asian (SAS)

AF:

0.00

AC:

AN:

84066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5634

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106234

Other (OTH)

AF:

0.00

AC:

AN:

59842

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.018

(source)

DANN

Benign

0.68

PhyloP100

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over