12-133227082-C-T

Variant names:

• chr12-133227082-C-T
• rs762774820
• NM_001372060.1:c.572G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001372060.1(ANHX):​c.572G>A​(p.Arg191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,535,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: ANHX NM_001372060.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372060.1. 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
	ANHX	NM_001372060.1	MANE Select	c.572G>A	p.Arg191His	missense	Exon 5 of 10	NP_001358989.1	A0A6E1YDD0
	ANHX	NM_001191054.1		c.572G>A	p.Arg191His	missense	Exon 5 of 9	NP_001177983.1	E9PGG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANHX	ENST00000545940.6	TSL:5 MANE Select	c.572G>A	p.Arg191His	missense	Exon 5 of 10	ENSP00000439513.2	A0A6E1YDD0
	ANHX	ENST00000419717.3	TSL:2	c.572G>A	p.Arg191His	missense	Exon 5 of 9	ENSP00000409950.1	E9PGG2
	ANHX	ENST00000673940.1		c.35G>A	p.Arg12His	missense	Exon 1 of 6	ENSP00000501263.1	A0A669KBG6

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152146 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000818 AC: 11 AN: 134452 AF XY: 0.0000410

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000208

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000167 AC: 231 AN: 1383748 Hom.: 0 Cov.: 31 AF XY: 0.000146 AC XY: 100 AN XY: 682826

African (AFR) AF: 0.0000633 AC: 2 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.000197 AC: 212 AN: 1078834

Other (OTH) AF: 0.000276 AC: 16 AN: 57900

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152146 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74316

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000553 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.018
FATHMM_MKL	Benign	0.086	N
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.7
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.84		Loss of sheet (P = 0.0315)
MVP		0.69
ClinPred		0.93	D
GERP RS		3.5
PromoterAI		-0.0054	Neutral
Varity_R		0.21
gMVP		0.50
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs762774820; hg19: chr12-133803668;