rs2373396

chr7-88794801-C-G

Variant summary

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

The NM_152706.4(TEX47):c.142G>C(p.Asp48His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,613,358 control chromosomes in the GnomAD database, including 18,049 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2048 hom., cov: 32)
  • Exomes 𝑓: 0.15 (16001 hom.)
• Consequence: TEX47 NM_152706.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

Genes affected

TEX47 (HGNC:22402): (testis expressed 47)

ZNF804B (HGNC:21958): (zinc finger protein 804B) Predicted to enable metal ion binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014933348).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX47	NM_152706.4	c.142G>C	p.Asp48His	missense_variant	2/2	ENST00000297203.3
ZNF804B	NM_181646.5	c.108+34717C>G		intron_variant		ENST00000333190.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX47	ENST00000297203.3	c.142G>C	p.Asp48His	missense_variant	2/2	1	NM_152706.4	P1
ZNF804B	ENST00000333190.5	c.108+34717C>G		intron_variant		1	NM_181646.5	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24591 AN: 151938 Hom.: 2044 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.0822

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.139 AC: 34822 AN: 250848 Hom.: 2610 AF XY: 0.136 AC XY: 18429 AN XY: 135584

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.0889

Gnomad SAS exome AF: 0.0791

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.145 AC: 212138 AN: 1461302 Hom.: 16001 Cov.: 34 AF XY: 0.143 AC XY: 104110 AN XY: 726960

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0917

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.162 AC: 24613 AN: 152056 Hom.: 2048 Cov.: 32 AF XY: 0.160 AC XY: 11903 AN XY: 74288

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0947

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.185

Alfa AF: 0.147 Hom.: 1256

Bravo AF: 0.165

TwinsUK AF: 0.150 AC: 558

ALSPAC AF: 0.155 AC: 596

ESP6500AA AF: 0.213 AC: 938

ESP6500EA AF: 0.148 AC: 1274

ExAC AF: 0.142 AC: 17207

Asia WGS AF: 0.118 AC: 414 AN: 3478

EpiCase AF: 0.156

EpiControl AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.87
Dann	Benign	0.52
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	0.98	P;P
PROVEAN	Benign	5.8	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MPC		0.053
ClinPred		0.0042	T
GERP RS		-2.0
Varity_R		0.035
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2373396; hg19: chr7-88424115; COSMIC: COSV51879108;