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:):

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	Protein	UniProt
TEX38	NM_001145474.4	c.312T>G	p.Asp104Glu	missense_variant	2/2	ENST00000334122.5	NP_001138946.1
TEX38	NM_001300863.2	c.150T>G	p.Asp50Glu	missense_variant	2/2		NP_001287792.1
TEX38	NM_001300864.2	c.84T>G	p.Asp28Glu	missense_variant	2/2		NP_001287793.1
TEX38	XM_011541421.4	c.315T>G	p.Asp105Glu	missense_variant	2/2		XP_011539723.1

Ensembl

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

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
MutationAssessor	Benign	-1.6	.;N;.;.
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;