4-945299-C-T

Variant names:

• chr4-945299-C-T
• rs6599388
• NM_032326.4:c.-31-2410C>T

Variant summary

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

The NM_032326.4(TMEM175):​c.-31-2410C>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
• Publications: 44 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=-0.97).
• 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 rank	MANE	Protein	UniProt
TMEM175	NM_032326.4	c.-31-2410C>T		intron_variant	Intron 1 of 10	ENST00000264771.9	NP_115702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM175	ENST00000264771.9	c.-31-2410C>T		intron_variant	Intron 1 of 10	1	NM_032326.4	ENSP00000264771.4

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

African (AFR) AF: 0.223 AC: 9204 AN: 41322

American (AMR) AF: 0.235 AC: 3575 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3466

East Asian (EAS) AF: 0.440 AC: 2179 AN: 4956

South Asian (SAS) AF: 0.443 AC: 2120 AN: 4786

European-Finnish (FIN) AF: 0.263 AC: 2770 AN: 10532

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19693 AN: 67776

Other (OTH) AF: 0.296 AC: 623 AN: 2104

Alfa AF: 0.297 Hom.: 3334

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
PhyloP100		-0.72
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: rs6599388; hg19: chr4-939087;