9-93954983-T-G

Position:

• chr9-93954983-T-G

Variant summary

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

The NM_021570.4(BARX1):​c.164A>C​(p.Glu55Ala) 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: 33)
• Consequence: BARX1 NM_021570.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

Genes affected

BARX1 (HGNC:955): (BARX homeobox 1) This gene encodes a member of the Bar subclass of homeobox transcription factors. Studies of the mouse and chick homolog suggest the encoded protein may play a role in developing teeth and craniofacial mesenchyme of neural crest origin. The protein may also be associated with differentiation of stomach epithelia. [provided by RefSeq, Jul 2008]

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	UniProt
BARX1	NM_021570.4	c.164A>C	p.Glu55Ala	missense_variant	1/4	ENST00000253968.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BARX1	ENST00000253968.11	c.164A>C	p.Glu55Ala	missense_variant	1/4	1	NM_021570.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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 06, 2021

The c.164A>C (p.E55A) alteration is located in exon 1 (coding exon 1) of the BARX1 gene. This alteration results from a A to C substitution at nucleotide position 164, causing the glutamic acid (E) at amino acid position 55 to be replaced by an alanine (A). 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	Uncertain	0.36
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.065
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.39
Sift	Benign	0.10	T
Sift4G	Benign	0.40	T
Polyphen		0.82	P
Vest4		0.26
MutPred		0.33		Loss of ubiquitination at K58 (P = 0.077);
MVP		0.84
MPC		1.4
ClinPred		0.76	D
GERP RS		3.7
Varity_R		0.16
gMVP		0.44

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: chr9-96717265;