Variant 12-133227906-C-T 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.419G>A(p.Ser140Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,531,564 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ANHX
NM_001372060.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00400

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=0.07834223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANHX	NM_001372060.1 linkuse as main transcript	c.419G>A	p.Ser140Asn	missense_variant	4/10	ENST00000545940.6	NP_001358989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANHX	ENST00000545940.6 linkuse as main transcript	c.419G>A	p.Ser140Asn	missense_variant	4/10	5	NM_001372060.1	ENSP00000439513.2		A0A6E1YDD0
ANHX	ENST00000419717.3 linkuse as main transcript	c.419G>A	p.Ser140Asn	missense_variant	4/9	2		ENSP00000409950.1		E9PGG2

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149596

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1381968

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681990

show subpopulations

Gnomad4 AFR exome

AF:

0.0000634

Gnomad4 AMR exome

AF:

0.00

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:

0.0000173

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72842

show subpopulations

Gnomad4 AFR

AF:

0.0000495

Gnomad4 AMR

AF:

0.00

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:

0.00

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

Dec 12, 2023

The c.419G>A (p.S140N) alteration is located in exon 4 (coding exon 3) of the ANHX gene. This alteration results from a G to A substitution at nucleotide position 419, causing the serine (S) at amino acid position 140 to be replaced by an asparagine (N). 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

0.17

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.031

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.59

T;.

M_CAP

Benign

0.058

MetaRNN

Benign

0.078

T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

2.0

M;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.17

Sift

Benign

0.040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.036

B;B

Vest4

0.10

MutPred

0.26

Loss of phosphorylation at S140 (P = 0.0292);Loss of phosphorylation at S140 (P = 0.0292);

MVP

0.41

ClinPred

0.44

GERP RS

2.1

Varity_R

0.11

gMVP

0.18

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