7-157009949-AGCGGCGGCGGCGGCGGCG-AGCGGCGGCG

Variant names:

• chr7-157009949-AGCGGCGGCG-A
• rs548755417
• NM_005515.4:c.393_401delCGCCGCCGC

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS1

The NM_005515.4(MNX1):​c.393_401delCGCCGCCGC​(p.Ala132_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 0.000166 in 908,220 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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 -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005515.4
• BP6: Variant 7-157009949-AGCGGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCGGCG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1651300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000185 (24/129774) while in subpopulation EAS AF = 0.00193 (8/4146). AF 95% confidence interval is 0.000959. There are 0 homozygotes in GnomAd4. There are 7 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005515.4. 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.393_401delCGCCGCCGC	p.Ala132_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.393_401delCGCCGCCGC	p.Ala132_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000252971.5
	MNX1-AS1	ENST00000818900.1		n.296+1925_296+1933delGGCGGCGGC		intron	N/A
	MNX1-AS1	ENST00000818901.1		n.50+840_50+848delGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 24 AN: 129766 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000742

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000215

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.000163 AC: 127 AN: 778446 Hom.: 1 AF XY: 0.000124 AC XY: 45 AN XY: 363696

African (AFR) AF: 0.000135 AC: 2 AN: 14820

American (AMR) AF: 0.00 AC: 0 AN: 1346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4992

East Asian (EAS) AF: 0.00116 AC: 5 AN: 4308

South Asian (SAS) AF: 0.000185 AC: 3 AN: 16176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1340

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

European-Non Finnish (NFE) AF: 0.000120 AC: 85 AN: 707932

Other (OTH) AF: 0.00123 AC: 32 AN: 25946

GnomAD4 genome AF: 0.000185 AC: 24 AN: 129774 Hom.: 0 Cov.: 0 AF XY: 0.000111 AC XY: 7 AN XY: 62922

African (AFR) AF: 0.0000285 AC: 1 AN: 35094

American (AMR) AF: 0.0000741 AC: 1 AN: 13498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3214

East Asian (EAS) AF: 0.00193 AC: 8 AN: 4146

South Asian (SAS) AF: 0.00 AC: 0 AN: 3814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6688

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

European-Non Finnish (NFE) AF: 0.000215 AC: 13 AN: 60514

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

Alfa AF: 0.00 Hom.: 1464

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Currarino triad (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;