rs1051613

Positions:

• chr4-957391-G-A
• chr4-957391-G-C

Variant summary

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

The ENST00000264771.9(TMEM175):​c.843-433G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,110 control chromosomes in the GnomAD database, including 21,971 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 0.53 (21971 hom., cov: 33)
• Consequence: TMEM175 ENST00000264771.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM175	NM_032326.4	c.843-433G>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.843-433G>A		intron_variant		1	NM_032326.4	ENSP00000264771	P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80655 AN: 151990 Hom.: 21940 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.531 AC: 80735 AN: 152110 Hom.: 21971 Cov.: 33 AF XY: 0.528 AC XY: 39242 AN XY: 74350

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.550

Alfa AF: 0.534 Hom.: 23335

Bravo AF: 0.528

Asia WGS AF: 0.405 AC: 1407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.33

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: rs1051613; hg19: chr4-951179;