chr17-43661455-G-A

Variant names:

• chr17-43661455-G-A
• rs9898682
• NM_004527.4:c.80C>T

Variant summary

Our verdict is Benign. The variant received -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 (★★). 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:6
• Conservation: PhyloP100: 4.08
• Publications: 21 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• isolated Klippel-Feil syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 259424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
MEOX1	NM_004527.4	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3	ENST00000318579.9	NP_004518.1
MEOX1	NM_013999.4	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 2		NP_054705.1
MEOX1	XM_011524818.3	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3		XP_011523120.1
MEOX1	NM_001040002.2	c.-204-62C>T		intron_variant	Intron 1 of 3		NP_001035091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEOX1	ENST00000318579.9	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 3	1	NM_004527.4	ENSP00000321684.4
MEOX1	ENST00000549132.2	c.80C>T	p.Ser27Leu	missense_variant	Exon 1 of 2	1		ENSP00000449049.2
MEOX1	ENST00000393661.2	c.-204-62C>T		intron_variant	Intron 1 of 3	3		ENSP00000377271.2

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

GnomAD2 exomes AF: 0.103 AC: 24847 AN: 242056 AF XY: 0.101

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 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

African (AFR) AF: 0.327 AC: 10908 AN: 33406

American (AMR) AF: 0.0536 AC: 2381 AN: 44438

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 2549 AN: 26008

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39668

South Asian (SAS) AF: 0.0858 AC: 7363 AN: 85794

European-Finnish (FIN) AF: 0.125 AC: 6637 AN: 53100

Middle Eastern (MID) AF: 0.0997 AC: 505 AN: 5066

European-Non Finnish (NFE) AF: 0.104 AC: 115663 AN: 1110866

Other (OTH) AF: 0.105 AC: 6327 AN: 60218

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

African (AFR) AF: 0.322 AC: 13331 AN: 41340

American (AMR) AF: 0.0753 AC: 1152 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5164

South Asian (SAS) AF: 0.0710 AC: 343 AN: 4828

European-Finnish (FIN) AF: 0.137 AC: 1451 AN: 10576

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7421 AN: 67942

Other (OTH) AF: 0.126 AC: 264 AN: 2102

Alfa AF: 0.121 Hom.: 3648

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		4.1
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
PromoterAI		-0.032	Neutral
Varity_R		0.31
gMVP		0.39
Mutation Taster		=62/38	polymorphism (auto)

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