14-105529779-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025268.4(TMEM121):​c.945C>A​(p.Asp315Glu) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMEM121
NM_025268.4 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43
Variant links:
Genes affected
TMEM121 (HGNC:20511): (transmembrane protein 121) 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.028432518).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM121NM_025268.4 linkuse as main transcriptc.945C>A p.Asp315Glu missense_variant 2/2 ENST00000392519.7 NP_079544.1 Q9BTD3
TMEM121NM_001331238.2 linkuse as main transcriptc.945C>A p.Asp315Glu missense_variant 2/2 NP_001318167.1 Q9BTD3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM121ENST00000392519.7 linkuse as main transcriptc.945C>A p.Asp315Glu missense_variant 2/21 NM_025268.4 ENSP00000376304.2 Q9BTD3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1307134
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
643262
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 05, 2024The c.945C>A (p.D315E) alteration is located in exon 2 (coding exon 1) of the TMEM121 gene. This alteration results from a C to A substitution at nucleotide position 945, causing the aspartic acid (D) at amino acid position 315 to be replaced by a glutamic acid (E). 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
0.10
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
1.3
DANN
Benign
0.93
DEOGEN2
Benign
0.034
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.54
.;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.028
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N;N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.23
N;N
REVEL
Benign
0.049
Sift
Benign
0.61
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0020
B;B
Vest4
0.044
MutPred
0.083
Gain of glycosylation at P312 (P = 0.1985);Gain of glycosylation at P312 (P = 0.1985);
MVP
0.092
MPC
1.1
ClinPred
0.12
T
GERP RS
0.74
Varity_R
0.045
gMVP
0.12

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: chr14-105996116; API