7-27095658-G-C

Position:

• chr7-27095658-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005522.5(HOXA1):​c.255C>G​(p.Asn85Lys) variant causes a missense 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXA1 NM_005522.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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]

HOTAIRM1 (HGNC:37117): (HOXA transcript antisense RNA, myeloid-specific 1) This non-coding locus is located in the HOX gene cluster. Transcription of this locus is induced by retinoic acid, and transcripts likely function in regulation of myelopoiesis through transcriptional activation of several genes in the HOXA cluster, in addition to several beta-2 integrins. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19319725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA1	NM_005522.5	c.255C>G	p.Asn85Lys	missense_variant	1/2	ENST00000643460.2	NP_005513.2
HOXA1	NM_153620.3	c.255C>G	p.Asn85Lys	missense_variant	1/3		NP_705873.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA1	ENST00000643460.2	c.255C>G	p.Asn85Lys	missense_variant	1/2		NM_005522.5	ENSP00000494260.2
HOXA1	ENST00000355633.5	c.255C>G	p.Asn85Lys	missense_variant	1/3	1		ENSP00000347851.5
HOTAIRM1	ENST00000495032.1	n.12G>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bosley-Salih-Alorainy syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.88	.;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;.;D
REVEL	Benign	0.063
Sift	Benign	0.044	D;.;D
Sift4G	Benign	0.30	T;.;T
Polyphen		0.87	.;.;P
Vest4		0.39
MutPred		0.26		Gain of methylation at N85 (P = 0.0071);Gain of methylation at N85 (P = 0.0071);Gain of methylation at N85 (P = 0.0071);
MVP		0.65
MPC		1.2
ClinPred		0.42	T
GERP RS		1.4
gMVP		0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs886062259; hg19: chr7-27135277;