chr7-157009949-AGCGGCGGCGGCG-A

Variant names:

• chr7-157009949-AGCGGCGGCGGCG-A
• rs548755417
• NM_005515.4:c.390_401delCGCCGCCGCCGC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The ENST00000252971.11(MNX1):​c.390_401delCGCCGCCGCCGC​(p.Ala131_Ala134del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 908,244 control chromosomes in the GnomAD database, including 6 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (6 hom.)
• Consequence: MNX1 ENST00000252971.11 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.14
• Publications: 4 publications found

Genes affected

MNX1 (HGNC:4979): (motor neuron and pancreas homeobox 1) This gene encodes a nuclear protein, which contains a homeobox domain and is a transcription factor. Mutations in this gene result in Currarino syndrome, an autosomic dominant congenital malformation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

MNX1-AS1 (HGNC:48954): (MNX1 antisense RNA 1 (head to head))

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in ENST00000252971.11
• BP6: Variant 7-157009949-AGCGGCGGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCGGCGGCG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1644782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00197 (256/129774) while in subpopulation NFE AF = 0.00332 (201/60514). AF 95% confidence interval is 0.00294. There are 0 homozygotes in GnomAd4. There are 117 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000252971.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	NM_005515.4	MANE Select	c.390_401delCGCCGCCGCCGC	p.Ala131_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	NP_005506.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	ENST00000252971.11	TSL:1 MANE Select	c.390_401delCGCCGCCGCCGC	p.Ala131_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000252971.5
	MNX1-AS1	ENST00000818900.1		n.296+1922_296+1933delGGCGGCGGCGGC		intron	N/A
	MNX1-AS1	ENST00000818901.1		n.50+837_50+848delGGCGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 256 AN: 129766 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000371

Gnomad ASJ AF: 0.00124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.000748

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00332

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.00360 AC: 2805 AN: 778470 Hom.: 6 AF XY: 0.00354 AC XY: 1289 AN XY: 363714

African (AFR) AF: 0.000270 AC: 4 AN: 14820

American (AMR) AF: 0.000743 AC: 1 AN: 1346

Ashkenazi Jewish (ASJ) AF: 0.00120 AC: 6 AN: 4992

East Asian (EAS) AF: 0.00 AC: 0 AN: 4306

South Asian (SAS) AF: 0.000556 AC: 9 AN: 16176

European-Finnish (FIN) AF: 0.00373 AC: 5 AN: 1340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1586

European-Non Finnish (NFE) AF: 0.00386 AC: 2733 AN: 707952

Other (OTH) AF: 0.00181 AC: 47 AN: 25952

GnomAD4 genome AF: 0.00197 AC: 256 AN: 129774 Hom.: 0 Cov.: 0 AF XY: 0.00186 AC XY: 117 AN XY: 62922

African (AFR) AF: 0.00103 AC: 36 AN: 35094

American (AMR) AF: 0.000370 AC: 5 AN: 13498

Ashkenazi Jewish (ASJ) AF: 0.00124 AC: 4 AN: 3214

East Asian (EAS) AF: 0.00 AC: 0 AN: 4146

South Asian (SAS) AF: 0.00105 AC: 4 AN: 3814

European-Finnish (FIN) AF: 0.000748 AC: 5 AN: 6688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 230

European-Non Finnish (NFE) AF: 0.00332 AC: 201 AN: 60514

Other (OTH) AF: 0.000554 AC: 1 AN: 1806

Alfa AF: 0.000441 Hom.: 1464

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1
Mutation Taster		=189/11	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643;