rs79213434

chr17-43661524-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004527.4(MEOX1):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,564,174 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A4A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0076 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (14 hom.)
• Consequence: MEOX1 NM_004527.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.620

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=0.0019446313).
• BP6: Variant 17-43661524-G-A is Benign according to our data. Variant chr17-43661524-G-A is described in ClinVar as [Benign]. Clinvar id is 259423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0076 (1157/152176) while in subpopulation AFR AF= 0.0266 (1106/41518). AF 95% confidence interval is 0.0253. There are 15 homozygotes in gnomad4. There are 547 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEOX1	NM_004527.4	c.11C>T	p.Ala4Val	missense_variant	1/3	ENST00000318579.9
MEOX1	NM_013999.4	c.11C>T	p.Ala4Val	missense_variant	1/2
MEOX1	XM_011524818.3	c.11C>T	p.Ala4Val	missense_variant	1/3
MEOX1	NM_001040002.2	c.-204-131C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEOX1	ENST00000318579.9	c.11C>T	p.Ala4Val	missense_variant	1/3	1	NM_004527.4	P1
MEOX1	ENST00000549132.2	c.11C>T	p.Ala4Val	missense_variant	1/2	1
MEOX1	ENST00000393661.2	c.-204-131C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1152 AN: 152058 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00191 AC: 372 AN: 194438 Hom.: 1 AF XY: 0.00151 AC XY: 161 AN XY: 106648

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.000982

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000670

Gnomad SAS exome AF: 0.0000419

Gnomad FIN exome AF: 0.000339

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.000645

GnomAD4 exome AF: 0.000719 AC: 1015 AN: 1411998 Hom.: 14 Cov.: 35 AF XY: 0.000611 AC XY: 426 AN XY: 697580

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000260

Gnomad4 SAS exome AF: 0.0000870

Gnomad4 FIN exome AF: 0.000275

Gnomad4 NFE exome AF: 0.0000184

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00760 AC: 1157 AN: 152176 Hom.: 15 Cov.: 32 AF XY: 0.00735 AC XY: 547 AN XY: 74414

Gnomad4 AFR AF: 0.0266

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000945 Hom.: 3

Bravo AF: 0.00834

ESP6500AA AF: 0.0211 AC: 89

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00203 AC: 244

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	7.0
Dann	Benign	0.51
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.69	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.36	N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.82	N;N
REVEL	Benign	0.16
Sift	Benign	0.68	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0010	B;.
Vest4		0.031
MVP		0.77
MPC		0.10
ClinPred		0.0061	T
GERP RS		-1.8
Varity_R		0.034
gMVP		0.22

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: rs79213434; hg19: chr17-41738892; COSMIC: COSV59356887;