rs6599388

Positions:

• chr4-945299-C-T

Variant summary

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

The NM_032326.4(TMEM175):​c.-31-2410C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,340 control chromosomes in the GnomAD database, including 6,324 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 0.28 (6324 hom., cov: 31)
• Consequence: TMEM175 NM_032326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM175	NM_032326.4	c.-31-2410C>T		intron_variant		ENST00000264771.9	NP_115702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM175	ENST00000264771.9	c.-31-2410C>T		intron_variant		1	NM_032326.4	ENSP00000264771	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42418 AN: 151224 Hom.: 6330 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.280 AC: 42415 AN: 151340 Hom.: 6324 Cov.: 31 AF XY: 0.281 AC XY: 20762 AN XY: 73964

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.235

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.296

Alfa AF: 0.313 Hom.: 2965

Bravo AF: 0.271

Asia WGS AF: 0.461 AC: 1588 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.15
DANN	Benign	0.45

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: rs6599388; hg19: chr4-939087;