rs2373396

Variant names:

• chr7-88794801-C-G
• rs2373396
• NM_152706.4:c.142G>C

Variant summary

Our verdict is Benign. The variant received -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. 13/19 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 0.16 (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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152706.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX47	NM_152706.4	MANE Select	c.142G>C	p.Asp48His	missense	Exon 2 of 2	NP_689919.1
	ZNF804B	NM_181646.5	MANE Select	c.108+34717C>G		intron	N/A	NP_857597.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX47	ENST00000297203.3	TSL:1 MANE Select	c.142G>C	p.Asp48His	missense	Exon 2 of 2	ENSP00000297203.2
	ZNF804B	ENST00000333190.5	TSL:1 MANE Select	c.108+34717C>G		intron	N/A	ENSP00000329638.4

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

GnomAD2 exomes AF: 0.139 AC: 34822 AN: 250848 AF XY: 0.136

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 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

African (AFR) AF: 0.216 AC: 7209 AN: 33452

American (AMR) AF: 0.132 AC: 5916 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 3130 AN: 26118

East Asian (EAS) AF: 0.0917 AC: 3640 AN: 39688

South Asian (SAS) AF: 0.0769 AC: 6629 AN: 86226

European-Finnish (FIN) AF: 0.152 AC: 8097 AN: 53408

Middle Eastern (MID) AF: 0.150 AC: 861 AN: 5756

European-Non Finnish (NFE) AF: 0.151 AC: 167562 AN: 1111604

Other (OTH) AF: 0.151 AC: 9094 AN: 60368

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

African (AFR) AF: 0.208 AC: 8628 AN: 41494

American (AMR) AF: 0.155 AC: 2364 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3466

East Asian (EAS) AF: 0.0947 AC: 488 AN: 5152

South Asian (SAS) AF: 0.0833 AC: 402 AN: 4824

European-Finnish (FIN) AF: 0.146 AC: 1549 AN: 10578

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10181 AN: 67970

Other (OTH) AF: 0.185 AC: 390 AN: 2112

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 v4.9

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
PhyloP100		0.11
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2373396; hg19: chr7-88424115; COSMIC: COSV51879108;