NM_001372060.1:c.725G>T

Variant names:

• chr12-133226432-C-A
• rs866559228
• NM_001372060.1:c.725G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001372060.1(ANHX):​c.725G>T​(p.Arg242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,381,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANHX NM_001372060.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07331687).

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.725G>T	p.Arg242Leu	missense	Exon 6 of 10	NP_001358989.1	A0A6E1YDD0
	ANHX	NM_001191054.1		c.725G>T	p.Arg242Leu	missense	Exon 6 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.725G>T	p.Arg242Leu	missense	Exon 6 of 10	ENSP00000439513.2	A0A6E1YDD0
	ANHX	ENST00000419717.3	TSL:2	c.725G>T	p.Arg242Leu	missense	Exon 6 of 9	ENSP00000409950.1	E9PGG2
	ANHX	ENST00000673940.1		c.188G>T	p.Arg63Leu	missense	Exon 2 of 6	ENSP00000501263.1	A0A669KBG6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1381382 Hom.: 0 Cov.: 31 AF XY: 0.00000147 AC XY: 1 AN XY: 681458

African (AFR) AF: 0.00 AC: 0 AN: 31446

American (AMR) AF: 0.00 AC: 0 AN: 35362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25072

East Asian (EAS) AF: 0.00 AC: 0 AN: 35676

South Asian (SAS) AF: 0.0000253 AC: 2 AN: 79068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077402

Other (OTH) AF: 0.00 AC: 0 AN: 57764

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	0.12
DANN	Benign	0.85
DEOGEN2	Benign	0.0075	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.34	N
PhyloP100		-3.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.13
Sift	Benign	0.10	T
Sift4G	Benign	0.26	T
Polyphen		0.090	B
Vest4		0.14
MutPred		0.36		Loss of solvent accessibility (P = 0.1922)
MVP		0.37
ClinPred		0.20	T
GERP RS		-6.4
Varity_R		0.063
gMVP		0.16
Mutation Taster		=99/1	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: rs866559228; hg19: chr12-133803018;