NM_005522.5:c.*281C>G

Variant names:

• chr7-27094159-G-C
• rs1783761584
• NM_005522.5:c.*281C>G

Variant summary

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

The NM_005522.5(HOXA1):​c.*281C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 289,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: HOXA1 NM_005522.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.157
• Publications: 0 publications found

Genes affected

HOXA1 (HGNC:5099): (homeobox A1) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. Two transcript variants encoding two different isoforms have been found for this gene, with only one of the isoforms containing the homeodomain region. [provided by RefSeq, Jul 2008]

HOXA1 Gene-Disease associations (from GenCC):

• human HOXA1 syndromes

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Bosley-Salih-Alorainy syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005522.5. 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
	HOXA1	NM_005522.5	MANE Select	c.*281C>G		3_prime_UTR	Exon 2 of 2	NP_005513.2	P49639-1
	HOXA1	NM_153620.3		c.*672C>G		3_prime_UTR	Exon 3 of 3	NP_705873.3	P49639-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA1	ENST00000643460.2	MANE Select	c.*281C>G		3_prime_UTR	Exon 2 of 2	ENSP00000494260.2	P49639-1
	HOXA1	ENST00000355633.5	TSL:1	c.*672C>G		3_prime_UTR	Exon 3 of 3	ENSP00000347851.5	E7ERT8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000103 AC: 3 AN: 289920 Hom.: 0 Cov.: 0 AF XY: 0.00000654 AC XY: 1 AN XY: 153018

African (AFR) AF: 0.00 AC: 0 AN: 9036

American (AMR) AF: 0.00 AC: 0 AN: 13216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8796

East Asian (EAS) AF: 0.00 AC: 0 AN: 17252

South Asian (SAS) AF: 0.00 AC: 0 AN: 37746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1250

European-Non Finnish (NFE) AF: 0.0000175 AC: 3 AN: 171698

Other (OTH) AF: 0.00 AC: 0 AN: 16388

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Human HOXA1 syndromes (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.4
DANN	Benign	0.62
PhyloP100		0.16

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: rs1783761584; hg19: chr7-27133778;