8-97853094-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000603405.1(TMEM69P1):​n.160A>C 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 0.00000978 in 1,328,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000025 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM69P1	ENST00000603405.1	n.160A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
LAPTM4B	ENST00000521545.7	c.*1620T>G		downstream_gene_variant		1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.*1620T>G		downstream_gene_variant		1		ENSP00000402301.2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000255 AC: 3 AN: 1176628 Hom.: 0 Cov.: 19 AF XY: 0.00000335 AC XY: 2 AN XY: 597620

African (AFR) AF: 0.000111 AC: 3 AN: 27100

American (AMR) AF: 0.00 AC: 0 AN: 43052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24068

East Asian (EAS) AF: 0.00 AC: 0 AN: 37880

South Asian (SAS) AF: 0.00 AC: 0 AN: 78660

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 859446

Other (OTH) AF: 0.00 AC: 0 AN: 50370

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152172 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74348

African (AFR) AF: 0.000217 AC: 9 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.0
DANN	Benign	0.81
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;