12-133221317-C-G

Variant names:

• chr12-133221317-C-G
• rs905206165
• NM_001372060.1:c.1168G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001372060.1(ANHX):​c.1168G>C​(p.Val390Leu) 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 1,383,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. V390M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ANHX NM_001372060.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04616049).

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.1168G>C	p.Val390Leu	missense	Exon 8 of 10	NP_001358989.1	A0A6E1YDD0
	ANHX	NM_001191054.1		c.856G>C	p.Val286Leu	missense	Exon 7 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.1168G>C	p.Val390Leu	missense	Exon 8 of 10	ENSP00000439513.2	A0A6E1YDD0
	ANHX	ENST00000419717.3	TSL:2	c.856G>C	p.Val286Leu	missense	Exon 7 of 9	ENSP00000409950.1	E9PGG2
	ANHX	ENST00000673940.1		c.658G>C	p.Val220Leu	missense	Exon 4 of 6	ENSP00000501263.1	A0A669KBG6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383736 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 682808

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25176

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.00 AC: 0 AN: 79220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33888

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078868

Other (OTH) AF: 0.0000173 AC: 1 AN: 57896

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.014
DANN	Benign	0.52
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.7
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.011
Sift	Benign	0.18	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.11		Gain of phosphorylation at S285 (P = 0.1912)
MVP		0.040
ClinPred		0.062	T
GERP RS		-5.5
Varity_R		0.032
gMVP		0.089
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs905206165; hg19: chr12-133797903;