8-97853094-T-C

Variant names:

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

Variant summary

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

The ENST00000603405.1(TMEM69P1):​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: TMEM69P1 ENST00000603405.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 0 publications found

Genes affected

TMEM69P1 (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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000603405.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	NM_018407.6	MANE Select	c.*1620T>C		downstream_gene	N/A	NP_060877.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM69P1	ENST00000603405.1	TSL:6	n.160A>G		non_coding_transcript_exon	Exon 1 of 1
	LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.*1620T>C		downstream_gene	N/A	ENSP00000428409.1	Q86VI4-2
	LAPTM4B	ENST00000445593.6	TSL:1	c.*1620T>C		downstream_gene	N/A	ENSP00000402301.2	Q86VI4-3

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

African (AFR) AF: 0.164 AC: 4402 AN: 26912

American (AMR) AF: 0.0165 AC: 710 AN: 43048

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 469 AN: 24066

East Asian (EAS) AF: 0.0963 AC: 3643 AN: 37822

South Asian (SAS) AF: 0.0197 AC: 1553 AN: 78644

European-Finnish (FIN) AF: 0.0244 AC: 1241 AN: 50894

Middle Eastern (MID) AF: 0.0210 AC: 108 AN: 5142

European-Non Finnish (NFE) AF: 0.00840 AC: 7219 AN: 859114

Other (OTH) AF: 0.0254 AC: 1281 AN: 50348

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

African (AFR) AF: 0.175 AC: 7272 AN: 41534

American (AMR) AF: 0.0228 AC: 349 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3468

East Asian (EAS) AF: 0.111 AC: 575 AN: 5192

South Asian (SAS) AF: 0.0275 AC: 133 AN: 4830

European-Finnish (FIN) AF: 0.0261 AC: 277 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0106 AC: 719 AN: 68024

Other (OTH) AF: 0.0473 AC: 100 AN: 2114

Alfa AF: 0.0144 Hom.: 16

Bravo AF: 0.0687

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.8
DANN	Benign	0.80
PhyloP100		-0.32

Splicing

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

Other links and lift over

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