ENST00000603405.1:n.160A>G

Variant names:

• chr8-97853094-T-C
• rs10504982
• ENST00000603405.1:n.160A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000603405.1(ENSG00000270861):​n.160A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,328,262 control chromosomes in the GnomAD database, including 1,326 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 0.062 (678 hom., cov: 33)
  • Exomes 𝑓: 0.018 (648 hom.)
• Consequence: ENSG00000270861 ENST00000603405.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

Genes affected

ENSG00000270861 (HGNC:56807): (TMEM69 pseudogene 1)

LAPTM4B (HGNC:13646): (lysosomal protein transmembrane 4 beta) Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including negative regulation of macromolecule metabolic process; regulation of lysosomal membrane permeability; and regulation of lysosome organization. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM69P1		n.97853094T>C		intragenic_variant
LAPTM4B	NM_018407.6	c.*1620T>C		downstream_gene_variant		ENST00000521545.7	NP_060877.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000270861	ENST00000603405.1	n.160A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
LAPTM4B	ENST00000521545.7	c.*1620T>C		downstream_gene_variant		1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.*1620T>C		downstream_gene_variant		1		ENSP00000402301.2

Frequencies

GnomAD3 genomes AF: 0.0624 AC: 9490 AN: 152154 Hom.: 678 Cov.: 33

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0279

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0483

GnomAD4 exome AF: 0.0175 AC: 20626 AN: 1175990 Hom.: 648 Cov.: 19 AF XY: 0.0173 AC XY: 10350 AN XY: 597312

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0165

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.0963

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.0244

Gnomad4 NFE exome AF: 0.00840

Gnomad4 OTH exome AF: 0.0254

GnomAD4 genome AF: 0.0624 AC: 9507 AN: 152272 Hom.: 678 Cov.: 33 AF XY: 0.0625 AC XY: 4656 AN XY: 74464

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0275

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.00810 Hom.: 5

Bravo AF: 0.0687

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.8
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10504982; hg19: chr8-98865322; COSMIC: COSV71453890;