Variant 12-133219332-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372060.1(ANHX):c.1316C>G(p.Pro439Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,535,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

ANHX
NM_001372060.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0280

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:

ANHX (HGNC:):

ANHX links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10206345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANHX	NM_001372060.1 linkuse as main transcript	c.1316C>G	p.Pro439Arg	missense_variant	9/10	ENST00000545940.6	NP_001358989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ANHX	ENST00000545940.6 linkuse as main transcript	c.1316C>G	p.Pro439Arg	missense_variant	9/10	5	NM_001372060.1	ENSP00000439513.2	A0A6E1YDD0
ANHX	ENST00000419717.3 linkuse as main transcript	c.1004C>G	p.Pro335Arg	missense_variant	8/9	2		ENSP00000409950.1	E9PGG2
ANHX	ENST00000673940.1 linkuse as main transcript	c.806C>G	p.Pro269Arg	missense_variant	5/6			ENSP00000501263.1	A0A669KBG6

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.00000506

AC:

AN:

1382810

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

682342

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000519

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000957

Bravo

AF:

0.0000831

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.1004C>G (p.P335R) alteration is located in exon 8 (coding exon 7) of the ANHX gene. This alteration results from a C to G substitution at nucleotide position 1004, causing the proline (P) at amino acid position 335 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.43

T;.

M_CAP

Benign

0.0054

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.018

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.84

P;P

Vest4

0.14

MutPred

0.27

Gain of methylation at P335 (P = 0.0098);Gain of methylation at P335 (P = 0.0098);

MVP

0.24

ClinPred

0.22

GERP RS

0.42

Varity_R

0.069

gMVP

0.041

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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