chr4-957831-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate
The NM_032326.4(TMEM175):c.850A>G(p.Asn284Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000554 in 1,606,482 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 1 hom., cov: 34)
Exomes 𝑓: 0.00050 ( 4 hom. )
Consequence
TMEM175
NM_032326.4 missense
NM_032326.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 6.56
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008975238).
BP6
?
Variant 4-957831-A-G is Benign according to our data. Variant chr4-957831-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3067237.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM175 | NM_032326.4 | c.850A>G | p.Asn284Asp | missense_variant | 11/11 | ENST00000264771.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM175 | ENST00000264771.9 | c.850A>G | p.Asn284Asp | missense_variant | 11/11 | 1 | NM_032326.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00106 AC: 162AN: 152226Hom.: 1 Cov.: 34
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000918 AC: 224AN: 243940Hom.: 1 AF XY: 0.000878 AC XY: 116AN XY: 132166
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GnomAD4 exome AF: 0.000501 AC: 728AN: 1454138Hom.: 4 Cov.: 31 AF XY: 0.000500 AC XY: 361AN XY: 722700
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GnomAD4 genome ? AF: 0.00106 AC: 162AN: 152344Hom.: 1 Cov.: 34 AF XY: 0.00115 AC XY: 86AN XY: 74500
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TMEM175: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Benign
Sift
Benign
T;T;T;T;T;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
D;.;.;D;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at