Genetic Variant NM_001145474.4:c.359C>T (chr1-46673194-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001145474.4(TEX38):c.359C>T(p.Pro120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,398,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

TEX38
NM_001145474.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

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: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29396725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4 link	c.359C>T	p.Pro120Leu	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1	Q6PEX7C9W8M6
TEX38	NM_001300863.2 link	c.197C>T	p.Pro66Leu	missense_variant	Exon 2 of 2		NP_001287792.1	B7ZLT1
TEX38	NM_001300864.2 link	c.131C>T	p.Pro44Leu	missense_variant	Exon 2 of 2		NP_001287793.1	B7ZLT2
TEX38	XM_011541421.4 link	c.362C>T	p.Pro121Leu	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.359C>T	p.Pro120Leu	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1		Q6PEX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000192

AC:

AN:

156010

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000917

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000331

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1398740

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31590

American (AMR)

AF:

0.00

AC:

AN:

35656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25094

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35724

South Asian (SAS)

AF:

0.00

AC:

AN:

79156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078588

Other (OTH)

AF:

0.0000862

AC:

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.359C>T (p.P120L) alteration is located in exon 2 (coding exon 2) of the TEX38 gene. This alteration results from a C to T substitution at nucleotide position 359, causing the proline (P) at amino acid position 120 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;T;T;T

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.29

T;T;T;T

MutationAssessor

Benign

1.6

.;L;.;.

PhyloP100

1.6

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.8

D;D;D;D

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.94

.;P;.;.

Vest4

0.17, 0.16, 0.15

MVP

0.75

GERP RS

4.6

Varity_R

0.31

gMVP

0.30

Mutation Taster

=74/26

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001145474.4:c.359C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over