16-90040394-G-T

Variant names:

• chr16-90040394-G-T
• rs61734730
• NM_001481.3:c.1106G>T

Variant summary

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

The ENST00000268699.9(GAS8):​c.1106G>T​(p.Arg369Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R369C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GAS8 ENST00000268699.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

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]

URAHP (HGNC:):

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]

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: ENST00000268699.9. 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
	DRC4	NM_001481.3	MANE Select	c.1106G>T	p.Arg369Leu	missense	Exon 9 of 11	NP_001472.1
	DRC4	NM_001286209.2		c.1031G>T	p.Arg344Leu	missense	Exon 9 of 11	NP_001273138.1
	DRC4	NM_001286205.2		c.857G>T	p.Arg286Leu	missense	Exon 9 of 11	NP_001273134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS8	ENST00000268699.9	TSL:1 MANE Select	c.1106G>T	p.Arg369Leu	missense	Exon 9 of 11	ENSP00000268699.4
	URAHP	ENST00000409873.5	TSL:1	n.716C>A		non_coding_transcript_exon	Exon 5 of 5
	GAS8	ENST00000566266.5	TSL:1	n.*1066G>T		non_coding_transcript_exon	Exon 8 of 10	ENSP00000454343.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459228 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725640

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 85672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5664

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110890

Other (OTH) AF: 0.00 AC: 0 AN: 60268

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.67	T
PhyloP100		5.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.026	D
Polyphen		0.93	P
Vest4		0.73
MutPred		0.22		Loss of MoRF binding (P = 0.0432)
MVP		0.65
MPC		0.14
ClinPred		0.97	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.38
Mutation Taster		=78/22	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: rs61734730; hg19: chr16-90106802;