1-46673292-G-T

Variant names:

• chr1-46673292-G-T
• rs779149194
• NM_001145474.4:c.457G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145474.4(TEX38):​c.457G>T​(p.Val153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V153M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX38 NM_001145474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 1 publications found

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]

ACMG classification

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=0.13161072).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX38	NM_001145474.4	c.457G>T	p.Val153Leu	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1
TEX38	NM_001300863.2	c.295G>T	p.Val99Leu	missense_variant	Exon 2 of 2		NP_001287792.1
TEX38	NM_001300864.2	c.229G>T	p.Val77Leu	missense_variant	Exon 2 of 2		NP_001287793.1
TEX38	XM_011541421.4	c.460G>T	p.Val154Leu	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	c.457G>T	p.Val153Leu	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000639 AC: 1 AN: 156474 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000596

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000336 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0097	T;T;T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.13	T;T;T
MutationAssessor	Benign	1.2	L;.;.
PhyloP100		0.71
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.5	N;N;N
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0080	B;.;.
Vest4		0.092
MVP		0.64
GERP RS		3.1
Varity_R		0.078
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs779149194; hg19: chr1-47138964;