17-43661285-G-T

Variant names:

• chr17-43661285-G-T
• rs713993044
• NM_004527.4:c.250C>A

Variant summary

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

The NM_004527.4(MEOX1):​c.250C>A​(p.Gln84Lys) variant causes a missense change. 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: 32)
• 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=0.37458226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEOX1	NM_004527.4	c.250C>A	p.Gln84Lys	missense_variant	Exon 1 of 3	ENST00000318579.9	NP_004518.1
MEOX1	NM_013999.4	c.250C>A	p.Gln84Lys	missense_variant	Exon 1 of 2		NP_054705.1
MEOX1	XM_011524818.3	c.250C>A	p.Gln84Lys	missense_variant	Exon 1 of 3		XP_011523120.1
MEOX1	NM_001040002.2	c.-96C>A		5_prime_UTR_variant	Exon 2 of 4		NP_001035091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEOX1	ENST00000318579.9	c.250C>A	p.Gln84Lys	missense_variant	Exon 1 of 3	1	NM_004527.4	ENSP00000321684.4
MEOX1	ENST00000549132.2	c.250C>A	p.Gln84Lys	missense_variant	Exon 1 of 2	1		ENSP00000449049.2
MEOX1	ENST00000393661.2	c.-96C>A		5_prime_UTR_variant	Exon 2 of 4	3		ENSP00000377271.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248380 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134146

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.017	D;D
Sift4G	Benign	0.32	T;D
Polyphen		0.94	P;.
Vest4		0.38
MutPred		0.33		Gain of methylation at Q84 (P = 0.0023);Gain of methylation at Q84 (P = 0.0023);
MVP		0.95
MPC		0.28
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.50
gMVP		0.33

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;