5-73123642-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173490.8(TMEM171):​c.269A>T​(p.Gln90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TMEM171
NM_173490.8 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0490
Variant links:
Genes affected
TMEM171 (HGNC:27031): (transmembrane protein 171) Predicted to be integral component of 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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0310328).
BP6
Variant 5-73123642-A-T is Benign according to our data. Variant chr5-73123642-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3178957.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM171NM_173490.8 linkc.269A>T p.Gln90Leu missense_variant 2/4 ENST00000454765.7 NP_775761.4 Q8WVE6-1
TMEM171NM_001161342.3 linkc.269A>T p.Gln90Leu missense_variant 2/4 NP_001154814.1 Q8WVE6-2
TMEM171XM_011543156.2 linkc.269A>T p.Gln90Leu missense_variant 2/4 XP_011541458.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM171ENST00000454765.7 linkc.269A>T p.Gln90Leu missense_variant 2/41 NM_173490.8 ENSP00000415030.2 Q8WVE6-1
TMEM171ENST00000287773.5 linkc.269A>T p.Gln90Leu missense_variant 2/45 ENSP00000287773.5 Q8WVE6-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
40
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 12, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.12
DANN
Benign
0.66
DEOGEN2
Benign
0.0048
T;.
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.0078
N
LIST_S2
Benign
0.32
T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.031
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.1
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.080
N;N
REVEL
Benign
0.031
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.064
MutPred
0.33
Loss of disorder (P = 0.0197);Loss of disorder (P = 0.0197);
MVP
0.055
MPC
0.065
ClinPred
0.076
T
GERP RS
-10
Varity_R
0.037
gMVP
0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-72419469; API