rs1051613

Variant names:

• chr4-957391-G-A
• rs1051613
• NM_032326.4:c.843-433G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-957391-G-A
• chr4-957391-G-C

Variant summary

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

The NM_032326.4(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 NM_032326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMEM175	NM_032326.4	c.843-433G>A		intron_variant	Intron 10 of 10	ENST00000264771.9	NP_115702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM175	ENST00000264771.9	c.843-433G>A		intron_variant	Intron 10 of 10	1	NM_032326.4	ENSP00000264771.4

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

African (AFR) AF: 0.599 AC: 24880 AN: 41512

American (AMR) AF: 0.448 AC: 6848 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1346 AN: 5160

South Asian (SAS) AF: 0.496 AC: 2392 AN: 4818

European-Finnish (FIN) AF: 0.540 AC: 5715 AN: 10592

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36348 AN: 67966

Other (OTH) AF: 0.550 AC: 1162 AN: 2112

Alfa AF: 0.534 Hom.: 32389

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
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051613; hg19: chr4-951179;