7-27129998-T-G

Variant names:

• chr7-27129998-T-G
• rs6943542
• NM_153631.3:c.-389-2928A>C

Variant summary

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

The NM_153631.3(HOXA3):​c.-389-2928A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 35)
• Consequence: HOXA3 NM_153631.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 1 publications found

Genes affected

HOXA3 (HGNC:5104): (homeobox A3) 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. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA4 (HGNC:5105): (homeobox A4) 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. [provided by RefSeq, Jul 2008]

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

ENSG00000273433 (HGNC:):

HOXA-AS2 (HGNC:43745): (HOXA cluster antisense RNA 2) This gene produces a long non-coding RNA that promotes cell proliferation. This transcript may interact with enhancer of zeste homolog 2 Polycomb repressive complex to repress gene expression. [provided by RefSeq, Dec 2017]

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 (BayesDel_noAF=-0.44).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153631.3. 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
	HOXA3	NM_153631.3	MANE Select	c.-389-2928A>C		intron	N/A	NP_705895.1	O43365
	HOXA4	NM_002141.5	MANE Select	c.616+120A>C		intron	N/A	NP_002132.3
	HOXA3	NM_001384335.1		c.-505-2928A>C		intron	N/A	NP_001371264.1	O43365

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-2928A>C		intron	N/A	ENSP00000484411.1	O43365
	HOXA4	ENST00000360046.10	TSL:1 MANE Select	c.616+120A>C		intron	N/A	ENSP00000353151.5	Q00056
	HOXA4	ENST00000610970.1	TSL:1	c.616+120A>C		intron	N/A	ENSP00000479166.1	Q00056

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.76
PhyloP100		1.8
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs6943542; hg19: chr7-27169617;