chr7-27184805-C-T

Position:

• chr7-27184805-C-T

Variant summary

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

The NM_005523.6(HOXA11):​c.340G>A​(p.Val114Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXA11 NM_005523.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

Genes affected

HOXA11 (HGNC:5101): (homeobox A11) 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. This gene is involved in the regulation of uterine development and is required for female fertility. Mutations in this gene can cause radio-ulnar synostosis with amegakaryocytic thrombocytopenia. [provided by RefSeq, Jul 2008]

HOXA11-AS (HGNC:24957): (HOXA11 antisense RNA) This gene produces a long non-coding RNA in antisense to transcription of the homeobox A11 gene. This transcript may associate with chromatin factors such as Polycomb repressive complex and act as a sponge for microRNAs, thereby participating in the regulation of expression of target genes. High levels of this transcript may be associated with tumor progression. [provided by RefSeq, Dec 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA11	NM_005523.6	c.340G>A	p.Val114Ile	missense_variant	1/2	ENST00000006015.4	NP_005514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA11	ENST00000006015.4	c.340G>A	p.Val114Ile	missense_variant	1/2	1	NM_005523.6	ENSP00000006015	P1
HOXA11-AS	ENST00000520360.6	n.299C>T		non_coding_transcript_exon_variant	1/3	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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 15, 2023

The c.340G>A (p.V114I) alteration is located in exon 1 (coding exon 1) of the HOXA11 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the valine (V) at amino acid position 114 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.36	T
Polyphen		0.96	D
Vest4		0.35
MutPred		0.37		Loss of sheet (P = 0.0457);
MVP		0.62
MPC		0.75
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.14
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-27224424; COSMIC: COSV50055200; COSMIC: COSV50055200;