4-951437-A-G

Position:

• chr4-951437-A-G

Variant summary

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

The NM_032326.4(TMEM175):​c.342+179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,984 control chromosomes in the GnomAD database, including 17,613 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 0.47 (17613 hom., cov: 32)
• Consequence: TMEM175 NM_032326.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM175	NM_032326.4	c.342+179A>G		intron_variant		ENST00000264771.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM175	ENST00000264771.9	c.342+179A>G		intron_variant		1	NM_032326.4	P1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71790 AN: 151864 Hom.: 17577 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.473 AC: 71878 AN: 151984 Hom.: 17613 Cov.: 32 AF XY: 0.470 AC XY: 34936 AN XY: 74294

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.470

Alfa AF: 0.442 Hom.: 2388

Bravo AF: 0.472

Asia WGS AF: 0.464 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290404; hg19: chr4-945225; COSMIC: COSV53277049; COSMIC: COSV53277049;