1-46672945-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145474.4(TEX38):ā€‹c.110A>Gā€‹(p.His37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

TEX38
NM_001145474.4 missense

Scores

3
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87
Variant links:
Genes affected
TEX38 (HGNC:29589): (testis expressed 38) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
ATPAF1 (HGNC:18803): (ATP synthase mitochondrial F1 complex assembly factor 1) This gene encodes an assembly factor for the F(1) component of the mitochondrial ATP synthase. This protein binds specifically to the F1 beta subunit and is thought to prevent this subunit from forming nonproductive homooligomers during enzyme assembly. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEX38NM_001145474.4 linkuse as main transcriptc.110A>G p.His37Arg missense_variant 2/2 ENST00000334122.5 NP_001138946.1
TEX38XM_011541421.4 linkuse as main transcriptc.113A>G p.His38Arg missense_variant 2/2 XP_011539723.1
TEX38NM_001300863.2 linkuse as main transcriptc.-46-7A>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NP_001287792.1
TEX38NM_001300864.2 linkuse as main transcriptc.-40-79A>G intron_variant NP_001287793.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEX38ENST00000334122.5 linkuse as main transcriptc.110A>G p.His37Arg missense_variant 2/21 NM_001145474.4 ENSP00000455854 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
32
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:
0.00
Gnomad OTH
AF:
0.000479
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74330
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:
0.00
Gnomad4 OTH
AF:
0.000479

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 GeneticsOct 27, 2022The c.110A>G (p.H37R) alteration is located in exon 2 (coding exon 2) of the TEX38 gene. This alteration results from a A to G substitution at nucleotide position 110, causing the histidine (H) at amino acid position 37 to be replaced by an arginine (R). 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
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.076
T;T
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.65
T;T
M_CAP
Uncertain
0.29
D
MetaRNN
Uncertain
0.62
D;D
MutationAssessor
Benign
1.7
.;L
MutationTaster
Benign
1.0
D;D;D;N;N
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.5
D;D
Sift
Uncertain
0.016
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.99
.;D
Vest4
0.62
MVP
0.77
GERP RS
4.2
Varity_R
0.41
gMVP
0.61

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: rs1336616105; hg19: chr1-47138617; API