rs614486

Positions:

• chr1-46673147-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145474.4(TEX38):​c.312T>G​(p.Asp104Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,551,320 control chromosomes in the GnomAD database, including 84,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.40 (13954 hom., cov: 32)
  • Exomes 𝑓: 0.30 (70797 hom.)
• Consequence: TEX38 NM_001145474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.97336E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX38	NM_001145474.4	c.312T>G	p.Asp104Glu	missense_variant	2/2	ENST00000334122.5
TEX38	NM_001300863.2	c.150T>G	p.Asp50Glu	missense_variant	2/2
TEX38	NM_001300864.2	c.84T>G	p.Asp28Glu	missense_variant	2/2
TEX38	XM_011541421.4	c.315T>G	p.Asp105Glu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX38	ENST00000334122.5	c.312T>G	p.Asp104Glu	missense_variant	2/2	1	NM_001145474.4	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60701 AN: 151830 Hom.: 13896 Cov.: 32

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.376 AC: 58814 AN: 156336 Hom.: 12827 AF XY: 0.368 AC XY: 30511 AN XY: 82902

Gnomad AFR exome AF: 0.595

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.775

Gnomad SAS exome AF: 0.381

Gnomad FIN exome AF: 0.290

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.299 AC: 418200 AN: 1399372 Hom.: 70797 Cov.: 39 AF XY: 0.300 AC XY: 207254 AN XY: 690202

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.458

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.380

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.400 AC: 60823 AN: 151948 Hom.: 13954 Cov.: 32 AF XY: 0.407 AC XY: 30268 AN XY: 74278

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.408

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.413

Alfa AF: 0.302 Hom.: 19927

Bravo AF: 0.420

TwinsUK AF: 0.251 AC: 932

ALSPAC AF: 0.263 AC: 1014

ESP6500AA AF: 0.590 AC: 817

ESP6500EA AF: 0.273 AC: 868

ExAC AF: 0.338 AC: 8673

Asia WGS AF: 0.604 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.47
DANN	Benign	0.63
DEOGEN2	Benign	0.0024	T;T;T;T
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.13	T;T;T;T
MetaRNN	Benign	0.0000010	T;T;T;T
MutationTaster	Benign	0.97	P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.74	N;N;N;N
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;.;.
Vest4		0.010, 0.039, 0.013
GERP RS		1.4
Varity_R		0.021
gMVP		0.040

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

LitVar

Other links and lift over

dbSNP: rs614486; hg19: chr1-47138819; COSMIC: COSV61304915; COSMIC: COSV61304915;