dbSNP rs1294526577: TEX38:p.Glu6Asp (chr1-46671952-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001145474.4(TEX38):c.18G>C(p.Glu6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,545,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

TEX38
NM_001145474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054703504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4 link	c.18G>C	p.Glu6Asp	missense_variant	Exon 1 of 2	ENST00000334122.5	NP_001138946.1	Q6PEX7C9W8M6
TEX38	NM_001300863.2 link	c.-66G>C		5_prime_UTR_variant	Exon 1 of 2		NP_001287792.1	B7ZLT1
TEX38	NM_001300864.2 link	c.-60G>C		5_prime_UTR_variant	Exon 1 of 2		NP_001287793.1	B7ZLT2
TEX38	XM_011541421.4 link	c.41-921G>C		intron_variant	Intron 1 of 1		XP_011539723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5 link	c.18G>C	p.Glu6Asp	missense_variant	Exon 1 of 2	1	NM_001145474.4	ENSP00000455854.1		Q6PEX7

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

150326

AF XY:

0.0000125

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000280

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000718

AC:

AN:

1393190

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

686456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31442

American (AMR)

AF:

0.00

AC:

AN:

35122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24886

East Asian (EAS)

AF:

0.000281

AC:

AN:

35568

South Asian (SAS)

AF:

0.00

AC:

AN:

78366

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1075362

Other (OTH)

AF:

0.00

AC:

AN:

57662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.18G>C (p.E6D) alteration is located in exon 1 (coding exon 1) of the TEX38 gene. This alteration results from a G to C substitution at nucleotide position 18, causing the glutamic acid (E) at amino acid position 6 to be replaced by an aspartic acid (D). 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

0.16

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.47

M_CAP

Benign

0.0071

MetaRNN

Benign

0.055

MutationAssessor

Benign

1.5

PhyloP100

0.049

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.95

Sift

Benign

0.060

Sift4G

Benign

0.10

Polyphen

0.0040

Vest4

0.043

MVP

0.30

GERP RS

1.5

PromoterAI

0.011

Neutral

(source)

Varity_R

0.12

gMVP

0.027

Mutation Taster

=97/3

polymorphism

(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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rs1294526577

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