rs9898682

chr17-43661455-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004527.4(MEOX1):c.80C>T(p.Ser27Leu) variant causes a missense change. The variant allele was found at a frequency of 0.11 in 1,610,480 control chromosomes in the GnomAD database, including 12,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. S27S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.16 (2822 hom., cov: 31)
  • Exomes 𝑓: 0.10 (9389 hom.)
• Consequence: MEOX1 NM_004527.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.08

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0013354421).
• BP6: Variant 17-43661455-G-A is Benign according to our data. Variant chr17-43661455-G-A is described in ClinVar as [Benign]. Clinvar id is 259424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-43661455-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEOX1	NM_004527.4	c.80C>T	p.Ser27Leu	missense_variant	1/3	ENST00000318579.9
MEOX1	NM_013999.4	c.80C>T	p.Ser27Leu	missense_variant	1/2
MEOX1	XM_011524818.3	c.80C>T	p.Ser27Leu	missense_variant	1/3
MEOX1	NM_001040002.2	c.-204-62C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEOX1	ENST00000318579.9	c.80C>T	p.Ser27Leu	missense_variant	1/3	1	NM_004527.4	P1
MEOX1	ENST00000549132.2	c.80C>T	p.Ser27Leu	missense_variant	1/2	1
MEOX1	ENST00000393661.2	c.-204-62C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24339 AN: 151798 Hom.: 2817 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0755

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.103 AC: 24847 AN: 242056 Hom.: 1884 AF XY: 0.101 AC XY: 13315 AN XY: 131940

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.0505

Gnomad ASJ exome AF: 0.0974

Gnomad EAS exome AF: 0.000277

Gnomad SAS exome AF: 0.0828

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0950

GnomAD4 exome AF: 0.104 AC: 152340 AN: 1458564 Hom.: 9389 Cov.: 36 AF XY: 0.104 AC XY: 75212 AN XY: 725354

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.0536

Gnomad4 ASJ exome AF: 0.0980

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0858

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.160 AC: 24364 AN: 151916 Hom.: 2822 Cov.: 31 AF XY: 0.158 AC XY: 11701 AN XY: 74266

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.0753

Gnomad4 ASJ AF: 0.0995

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0710

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.126

Alfa AF: 0.115 Hom.: 2113

Bravo AF: 0.161

TwinsUK AF: 0.108 AC: 402

ALSPAC AF: 0.102 AC: 394

ESP6500AA AF: 0.302 AC: 1313

ESP6500EA AF: 0.101 AC: 857

ExAC AF: 0.109 AC: 13196

Asia WGS AF: 0.0420 AC: 147 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T;T
MetaRNN	Benign	0.0013	T;T
MetaSVM	Benign	-1.3	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	0.00047	P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		0.71	P;.
Vest4		0.059
MPC		0.090
ClinPred		0.090	T
GERP RS		4.7
Varity_R		0.31
gMVP		0.39

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: rs9898682; hg19: chr17-41738823; COSMIC: COSV59356702;