rs614486

Variant names:

• chr1-46673147-T-G
• rs614486
• NM_001145474.4:c.312T>G

Variant summary

Our verdict is Benign. The variant received -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.

• 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
• Publications: 24 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
TEX38	NM_001145474.4	c.312T>G	p.Asp104Glu	missense_variant	Exon 2 of 2	ENST00000334122.5	NP_001138946.1
TEX38	NM_001300863.2	c.150T>G	p.Asp50Glu	missense_variant	Exon 2 of 2		NP_001287792.1
TEX38	NM_001300864.2	c.84T>G	p.Asp28Glu	missense_variant	Exon 2 of 2		NP_001287793.1
TEX38	XM_011541421.4	c.315T>G	p.Asp105Glu	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.312T>G	p.Asp104Glu	missense_variant	Exon 2 of 2	1	NM_001145474.4	ENSP00000455854.1

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

GnomAD2 exomes AF: 0.376 AC: 58814 AN: 156336 AF XY: 0.368

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 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

African (AFR) AF: 0.602 AC: 19018 AN: 31598

American (AMR) AF: 0.458 AC: 16356 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 8949 AN: 25178

East Asian (EAS) AF: 0.784 AC: 28001 AN: 35738

South Asian (SAS) AF: 0.380 AC: 30139 AN: 79234

European-Finnish (FIN) AF: 0.286 AC: 14081 AN: 49264

Middle Eastern (MID) AF: 0.360 AC: 2053 AN: 5698

European-Non Finnish (NFE) AF: 0.259 AC: 279328 AN: 1078952

Other (OTH) AF: 0.350 AC: 20275 AN: 58008

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

African (AFR) AF: 0.583 AC: 24132 AN: 41400

American (AMR) AF: 0.452 AC: 6906 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.779 AC: 3999 AN: 5136

South Asian (SAS) AF: 0.408 AC: 1959 AN: 4802

European-Finnish (FIN) AF: 0.293 AC: 3109 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18254 AN: 67956

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.321 Hom.: 34240

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
MutationAssessor	Benign	-1.6	.;N;.;.
PhyloP100		-0.045
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
Mutation Taster		=100/0	polymorphism (auto)

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