rs6599389

Positions:

• chr4-945325-G-A
• chr4-945325-G-T

Variant summary

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

The ENST00000264771.9(TMEM175):​c.-31-2384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 151,922 control chromosomes in the GnomAD database, including 518 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 0.061 (518 hom., cov: 32)
• Consequence: TMEM175 ENST00000264771.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

TMEM175 (HGNC:28709): (transmembrane protein 175) Enables potassium ion leak channel activity. Involved in potassium ion transmembrane transport. Located in endosome and lysosome. Is integral component of endosome membrane and integral component of lysosomal 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM175	NM_032326.4	c.-31-2384G>A		intron_variant		ENST00000264771.9	NP_115702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM175	ENST00000264771.9	c.-31-2384G>A		intron_variant		1	NM_032326.4	ENSP00000264771	P1

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9222 AN: 151804 Hom.: 522 Cov.: 32

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0506

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0509

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0606 AC: 9205 AN: 151922 Hom.: 518 Cov.: 32 AF XY: 0.0600 AC XY: 4456 AN XY: 74248

Gnomad4 AFR AF: 0.0141

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0725

Gnomad4 OTH AF: 0.0489

Alfa AF: 0.0810 Hom.: 899

Bravo AF: 0.0615

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs6599389; hg19: chr4-939113;