chr17-43661285-G-C

Position:

• chr17-43661285-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004527.4(MEOX1):​c.250C>G​(p.Gln84Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MEOX1 NM_004527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88

Genes affected

MEOX1 (HGNC:7013): (mesenchyme homeobox 1) This gene encodes a member of a subfamily of non-clustered, diverged, antennapedia-like homeobox-containing genes. The encoded protein may play a role in the molecular signaling network regulating somite development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34309903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEOX1	NM_004527.4	c.250C>G	p.Gln84Glu	missense_variant	1/3	ENST00000318579.9	NP_004518.1
MEOX1	NM_013999.4	c.250C>G	p.Gln84Glu	missense_variant	1/2		NP_054705.1
MEOX1	XM_011524818.3	c.250C>G	p.Gln84Glu	missense_variant	1/3		XP_011523120.1
MEOX1	NM_001040002.2	c.-96C>G		5_prime_UTR_variant	2/4		NP_001035091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEOX1	ENST00000318579.9	c.250C>G	p.Gln84Glu	missense_variant	1/3	1	NM_004527.4	ENSP00000321684	P1
MEOX1	ENST00000549132.2	c.250C>G	p.Gln84Glu	missense_variant	1/2	1		ENSP00000449049
MEOX1	ENST00000393661.2	c.-96C>G		5_prime_UTR_variant	2/4	3		ENSP00000377271

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458644 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.26
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.25	T;D
Polyphen		0.87	P;.
Vest4		0.38
MutPred		0.16		Gain of glycosylation at T82 (P = 0.0996);Gain of glycosylation at T82 (P = 0.0996);
MVP		0.94
MPC		0.13
ClinPred		0.83	D
GERP RS		4.7
Varity_R		0.35
gMVP		0.26

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: rs713993044; hg19: chr17-41738653;