1-46673056-G-A

Variant summary

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

The NM_001145474.4(TEX38):​c.221G>A​(p.Arg74His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,551,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TEX38
NM_001145474.4 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.475
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 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=0.00972423).
BP6
Variant 1-46673056-G-A is Benign according to our data. Variant chr1-46673056-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2460615.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TEX38NM_001145474.4 linkc.221G>A p.Arg74His missense_variant 2/2 ENST00000334122.5 NP_001138946.1 Q6PEX7C9W8M6
TEX38NM_001300863.2 linkc.59G>A p.Arg20His missense_variant 2/2 NP_001287792.1 B7ZLT1
TEX38XM_011541421.4 linkc.224G>A p.Arg75His missense_variant 2/2 XP_011539723.1
TEX38NM_001300864.2 linkc.-8G>A 5_prime_UTR_variant 2/2 NP_001287793.1 B7ZLT2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TEX38ENST00000334122.5 linkc.221G>A p.Arg74His missense_variant 2/21 NM_001145474.4 ENSP00000455854.1 Q6PEX7

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152190
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:
0.000962
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000115
AC:
18
AN:
156300
Hom.:
0
AF XY:
0.000133
AC XY:
11
AN XY:
82834
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00128
Gnomad SAS exome
AF:
0.0000878
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000165
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000307
AC:
43
AN:
1399424
Hom.:
0
Cov.:
31
AF XY:
0.0000319
AC XY:
22
AN XY:
690216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000672
Gnomad4 SAS exome
AF:
0.000114
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000278
Gnomad4 OTH exome
AF:
0.000103
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000962
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000529
ExAC
AF:
0.0000762
AC:
2

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 GeneticsFeb 28, 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
0.080
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
12
DANN
Benign
0.81
DEOGEN2
Benign
0.0040
T;T;T
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.66
T;T;T
M_CAP
Benign
0.0070
T
MetaRNN
Benign
0.0097
T;T;T
MutationAssessor
Benign
-0.63
.;N;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.35
N;N;N
Sift
Benign
0.51
T;T;T
Sift4G
Benign
0.51
T;T;T
Polyphen
0.0010
.;B;.
Vest4
0.062, 0.073
MVP
0.60
GERP RS
1.9
Varity_R
0.021
gMVP
0.076

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: rs774501380; hg19: chr1-47138728; COSMIC: COSV100236198; COSMIC: COSV100236198; API