1-46673445-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145474.4(TEX38):c.610T>A(p.Ser204Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,549,322 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 118 hom. )

Consequence

TEX38
NM_001145474.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.579

Publications

2 publications found

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]

TEX38 links:

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]

ATPAF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034383535).

BP6

Variant 1-46673445-T-A is Benign according to our data. Variant chr1-46673445-T-A is described in ClinVar as [Benign]. Clinvar id is 769513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00604 (920/152300) while in subpopulation EAS AF = 0.0335 (174/5190). AF 95% confidence interval is 0.0302. There are 10 homozygotes in GnomAd4. There are 497 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4 link	c.610T>A	p.Ser204Thr	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1	Q6PEX7C9W8M6
TEX38	NM_001300863.2 link	c.448T>A	p.Ser150Thr	missense_variant	Exon 2 of 2		NP_001287792.1	B7ZLT1
TEX38	NM_001300864.2 link	c.382T>A	p.Ser128Thr	missense_variant	Exon 2 of 2		NP_001287793.1	B7ZLT2
TEX38	XM_011541421.4 link	c.613T>A	p.Ser205Thr	missense_variant	Exon 2 of 2		XP_011539723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5 link	c.610T>A	p.Ser204Thr	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1		Q6PEX7

Frequencies

GnomAD3 genomes

AF:

0.00602

AC:

916

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.0136

AC:

2129

AN:

156080

AF XY:

0.0125

show subpopulations

Gnomad AFR exome

AF:

0.000736

Gnomad AMR exome

AF:

0.0483

Gnomad ASJ exome

AF:

0.00275

Gnomad EAS exome

AF:

0.0360

Gnomad FIN exome

AF:

0.000365

Gnomad NFE exome

AF:

0.000824

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

AF:

0.00414

AC:

5777

AN:

1397022

Hom.:

118

Cov.:

AF XY:

0.00440

AC XY:

3028

AN XY:

688782

show subpopulations

African (AFR)

AF:

0.000729

AC:

AN:

31570

American (AMR)

AF:

0.0475

AC:

1693

AN:

35626

Ashkenazi Jewish (ASJ)

AF:

0.00419

AC:

105

AN:

25030

East Asian (EAS)

AF:

0.0377

AC:

1345

AN:

35706

South Asian (SAS)

AF:

0.0190

AC:

1498

AN:

78996

European-Finnish (FIN)

AF:

0.000531

AC:

AN:

48924

Middle Eastern (MID)

AF:

0.00141

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.000652

AC:

702

AN:

1077458

Other (OTH)

AF:

0.00650

AC:

377

AN:

58024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

315

630

945

1260

1575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00604

AC:

920

AN:

152300

Hom.:

Cov.:

AF XY:

0.00667

AC XY:

497

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41558

American (AMR)

AF:

0.0326

AC:

499

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.0335

AC:

174

AN:

5190

South Asian (SAS)

AF:

0.0255

AC:

123

AN:

4832

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68018

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00263

Hom.:

Bravo

AF:

0.00850

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00126

AC:

ExAC

AF:

0.00633

AC:

164

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.011

T;T;T

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.39

T;T;T

MetaRNN

Benign

0.0034

T;T;T

MutationAssessor

Uncertain

2.1

M;.;.

PhyloP100

0.58

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.7

N;N;N

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.56

P;.;.

Vest4

0.10

GERP RS

3.9

Varity_R

0.10

gMVP

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-46673445-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over