chr4-945325-G-A

Variant names:

• chr4-945325-G-A
• rs6599389
• NM_032326.4:c.-31-2384G>A

Variant summary

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

The NM_032326.4(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 NM_032326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 45 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032326.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM175	NM_032326.4	MANE Select	c.-31-2384G>A		intron	N/A	NP_115702.1
	TMEM175	NM_001297423.2		c.-738-2384G>A		intron	N/A	NP_001284352.1
	TMEM175	NM_001297424.2		c.-54-5096G>A		intron	N/A	NP_001284353.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM175	ENST00000264771.9	TSL:1 MANE Select	c.-31-2384G>A		intron	N/A	ENSP00000264771.4
	TMEM175	ENST00000622959.3	TSL:1	c.-620-2384G>A		intron	N/A	ENSP00000485461.1
	TMEM175	ENST00000513952.5	TSL:1	n.-31-2384G>A		intron	N/A	ENSP00000427218.1

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

African (AFR) AF: 0.0141 AC: 583 AN: 41444

American (AMR) AF: 0.0502 AC: 766 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1490 AN: 5126

South Asian (SAS) AF: 0.133 AC: 639 AN: 4810

European-Finnish (FIN) AF: 0.0258 AC: 272 AN: 10534

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0725 AC: 4924 AN: 67960

Other (OTH) AF: 0.0489 AC: 103 AN: 2106

Alfa AF: 0.0750 Hom.: 1767

Bravo AF: 0.0615

Asia WGS AF: 0.176 AC: 613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.35
PhyloP100		1.4
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: rs6599389; hg19: chr4-939113;