dbSNP rs1224590758: TEX38:p.Arg56Lys (chr1-46673002-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145474.4(TEX38):c.167G>A(p.Arg56Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R56T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TEX38
NM_001145474.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.613

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14204574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4 link	c.167G>A	p.Arg56Lys	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1	Q6PEX7C9W8M6
TEX38	NM_001300863.2 link	c.5G>A	p.Arg2Lys	missense_variant	Exon 2 of 2		NP_001287792.1	B7ZLT1
TEX38	XM_011541421.4 link	c.170G>A	p.Arg57Lys	missense_variant	Exon 2 of 2		XP_011539723.1
TEX38	NM_001300864.2 link	c.-40-22G>A		intron_variant	Intron 1 of 1		NP_001287793.1	B7ZLT2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX38	ENST00000334122.5 link	c.167G>A	p.Arg56Lys	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1		Q6PEX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399400

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078966

Other (OTH)

AF:

0.00

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.086

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;T;T

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.14

T;T;T

MutationAssessor

Benign

1.4

.;L;.

PhyloP100

0.61

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;N;N

Sift

Benign

0.22

T;T;D

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0080

.;B;.

Vest4

0.15, 0.062

MVP

0.61

GERP RS

2.4

Varity_R

0.084

gMVP

0.46

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over