X-110171452-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032227.4(TMEM164):​c.619C>T​(p.Arg207Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000091 in 1,208,152 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 4 hem. )

Consequence

TMEM164
NM_032227.4 missense

Scores

3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
Variant links:
Genes affected
TMEM164 (HGNC:26217): (transmembrane protein 164) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14426693).
BS2
High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM164NM_032227.4 linkc.619C>T p.Arg207Trp missense_variant Exon 6 of 7 ENST00000372068.7 NP_115603.2 Q5U3C3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM164ENST00000372068.7 linkc.619C>T p.Arg207Trp missense_variant Exon 6 of 7 1 NM_032227.4 ENSP00000361138.2 Q5U3C3-1

Frequencies

GnomAD3 genomes
AF:
0.00000896
AC:
1
AN:
111651
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33821
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000221
AC:
4
AN:
181187
Hom.:
0
AF XY:
0.0000304
AC XY:
2
AN XY:
65689
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000542
Gnomad FIN exome
AF:
0.0000629
Gnomad NFE exome
AF:
0.0000247
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000912
AC:
10
AN:
1096501
Hom.:
0
Cov.:
29
AF XY:
0.0000111
AC XY:
4
AN XY:
361905
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000186
Gnomad4 FIN exome
AF:
0.0000247
Gnomad4 NFE exome
AF:
0.00000951
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000896
AC:
1
AN:
111651
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33821
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.619C>T (p.R207W) alteration is located in exon 6 (coding exon 5) of the TMEM164 gene. This alteration results from a C to T substitution at nucleotide position 619, causing the arginine (R) at amino acid position 207 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
.;T;T;.
FATHMM_MKL
Benign
0.65
D
LIST_S2
Uncertain
0.95
D;.;D;D
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-1.9
.;N;N;.
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.72
N;N;N;N
REVEL
Benign
0.078
Sift
Benign
0.041
D;D;D;T
Sift4G
Uncertain
0.046
D;D;D;D
Polyphen
0.0
.;B;B;B
Vest4
0.22
MVP
0.10
MPC
0.98
ClinPred
0.25
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376172046; hg19: chrX-109414680; COSMIC: COSV55811588; API