17-43661285-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 publications found

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]

MEOX1 Gene-Disease associations (from GenCC):

• Klippel-Feil syndrome 2, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• isolated Klippel-Feil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004527.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX1	NM_004527.4	MANE Select	c.250C>G	p.Gln84Glu	missense	Exon 1 of 3	NP_004518.1	P50221-1
	MEOX1	NM_013999.4		c.250C>G	p.Gln84Glu	missense	Exon 1 of 2	NP_054705.1	P50221-2
	MEOX1	NM_001040002.2		c.-96C>G		5_prime_UTR	Exon 2 of 4	NP_001035091.1	P50221-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEOX1	ENST00000318579.9	TSL:1 MANE Select	c.250C>G	p.Gln84Glu	missense	Exon 1 of 3	ENSP00000321684.4	P50221-1
	MEOX1	ENST00000549132.2	TSL:1	c.250C>G	p.Gln84Glu	missense	Exon 1 of 2	ENSP00000449049.2	P50221-2
	MEOX1	ENST00000909611.1		c.250C>G	p.Gln84Glu	missense	Exon 1 of 3	ENSP00000579670.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110110

Other (OTH) AF: 0.00 AC: 0 AN: 60272

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.26
Sift	Uncertain	0.010	D
Sift4G	Benign	0.25	T
Polyphen		0.87	P
Vest4		0.38
MutPred		0.16		Gain of glycosylation at T82 (P = 0.0996)
MVP		0.94
MPC		0.13
ClinPred		0.83	D
GERP RS		4.7
PromoterAI		-0.034	Neutral
Varity_R		0.35
gMVP		0.26
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs713993044; hg19: chr17-41738653;