Variant 12-133226965-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372060.1(ANHX):c.689C>G(p.Ser230Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,530,052 control chromosomes in the GnomAD database, including 33,294 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2469 hom., cov: 33)

Exomes 𝑓: 0.21 ( 30825 hom. )

Consequence

ANHX
NM_001372060.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

ANHX (HGNC:40024): (anomalous homeobox) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in eye development and regulation of transcription by RNA polymerase II. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ANHX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047139227).

BP6

Variant 12-133226965-G-C is Benign according to our data. Variant chr12-133226965-G-C is described in ClinVar as [Benign]. Clinvar id is 1296944.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANHX	NM_001372060.1 link	c.689C>G	p.Ser230Cys	missense_variant	5/10	ENST00000545940.6	NP_001358989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANHX	ENST00000545940.6 link	c.689C>G	p.Ser230Cys	missense_variant	5/10	5	NM_001372060.1	ENSP00000439513.2	A0A6E1YDD0
ANHX	ENST00000419717.3 link	c.689C>G	p.Ser230Cys	missense_variant	5/9	2		ENSP00000409950.1	E9PGG2
ANHX	ENST00000673940.1 link	c.152C>G	p.Ser51Cys	missense_variant	1/6			ENSP00000501263.1	A0A669KBG6

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24181

AN:

152056

Hom.:

2470

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.181

GnomAD3 exomes

AF:

0.177

AC:

23182

AN:

130698

Hom.:

2304

AF XY:

0.185

AC XY:

13169

AN XY:

71088

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0990

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.208

AC:

287102

AN:

1377878

Hom.:

30825

Cov.:

AF XY:

0.209

AC XY:

141725

AN XY:

679196

show subpopulations

Gnomad4 AFR exome

AF:

0.0333

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.219

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.159

AC:

24176

AN:

152174

Hom.:

2469

Cov.:

AF XY:

0.158

AC XY:

11722

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0387

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.216

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.212

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.180

Alfa

AF:

0.203

Hom.:

661

Bravo

AF:

0.147

TwinsUK

AF:

0.211

AC:

783

ALSPAC

AF:

0.214

AC:

824

ExAC

AF:

0.158

AC:

2764

Asia WGS

AF:

0.182

AC:

629

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2019	This variant is associated with the following publications: (PMID: 30679340) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0049

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.40

T;.

MetaRNN

Benign

0.0047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.25

Sift

Benign

0.070

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.98

D;D

Vest4

0.054

ClinPred

0.034

GERP RS

3.1

Varity_R

0.12

gMVP

0.24

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over