Genetic Variant TEX47:p.Phe22Ser (chr7-88794878-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152706.4(TEX47):c.65T>C(p.Phe22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000885 in 1,612,506 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 2 hom. )

Consequence

TEX47
NM_152706.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

2 publications found

Variant links:

Genes affected

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

TEX47 links:

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]

ZNF804B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005921006).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX47	NM_152706.4	MANE Select	c.65T>C	p.Phe22Ser	missense	Exon 2 of 2	NP_689919.1	Q8TBZ9
	ZNF804B	NM_181646.5	MANE Select	c.108+34794A>G		intron	N/A	NP_857597.1	A4D1E1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX47	ENST00000297203.3	TSL:1 MANE Select	c.65T>C	p.Phe22Ser	missense	Exon 2 of 2	ENSP00000297203.2	Q8TBZ9
	ZNF804B	ENST00000333190.5	TSL:1 MANE Select	c.108+34794A>G		intron	N/A	ENSP00000329638.4	A4D1E1

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.0362

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000522

AC:

130

AN:

249078

AF XY:

0.000534

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000896

AC:

1308

AN:

1460244

Hom.:

Cov.:

AF XY:

0.000869

AC XY:

631

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33320

American (AMR)

AF:

0.000180

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26030

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85882

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00111

AC:

1232

AN:

1111458

Other (OTH)

AF:

0.00101

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000782

AC:

119

AN:

152262

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

41568

American (AMR)

AF:

0.000262

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68008

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000848

Hom.:

Bravo

AF:

0.000990

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000461

AC:

EpiCase

AF:

0.000983

EpiControl

AF:

0.00119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.00093

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.21

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.99

PhyloP100

1.2

PROVEAN

Benign

0.37

REVEL

Benign

0.059

Sift

Uncertain

0.015

Sift4G

Benign

0.066

Polyphen

0.0

Vest4

0.041

MVP

0.17

MPC

0.074

ClinPred

0.018

GERP RS

0.89

Varity_R

0.084

gMVP

0.29

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over