10-123136207-C-A

Variant names:

• chr10-123136207-C-A
• rs1314128260
• NM_001105574.2:c.157C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001105574.2(HMX3):​c.157C>A​(p.Arg53Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,228,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: HMX3 NM_001105574.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683
• Publications: 0 publications found

Genes affected

HMX3 (HGNC:5019): (H6 family homeobox 3) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in ear development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including embryo implantation; maternal process involved in female pregnancy; and neuromuscular process controlling balance. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.683 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105574.2. 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
	HMX3	NM_001105574.2	MANE Select	c.157C>A	p.Arg53Arg	synonymous	Exon 1 of 2	NP_001099044.1	A6NHT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMX3	ENST00000357878.7	TSL:2 MANE Select	c.157C>A	p.Arg53Arg	synonymous	Exon 1 of 2	ENSP00000350549.4	A6NHT5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000244 AC: 3 AN: 1228570 Hom.: 0 Cov.: 36 AF XY: 0.00000499 AC XY: 3 AN XY: 600636

African (AFR) AF: 0.00 AC: 0 AN: 25054

American (AMR) AF: 0.00 AC: 0 AN: 15336

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17956

East Asian (EAS) AF: 0.00 AC: 0 AN: 29344

South Asian (SAS) AF: 0.00 AC: 0 AN: 45046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41864

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 1000304

Other (OTH) AF: 0.00 AC: 0 AN: 49530

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		0.68
PromoterAI		-0.0066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs1314128260; hg19: chr10-124895723;