7-157009949-AGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCG

Variant names:

• chr7-157009949-AGCGGCG-A
• rs548755417
• NM_005515.4:c.396_401delCGCCGC

Variant summary

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

The NM_005515.4(MNX1):​c.396_401delCGCCGC​(p.Ala133_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 0.0018 in 908,126 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0018 (4 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 2.71
• 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 NM_005515.4
• BP6: Variant 7-157009949-AGCGGCG-A is Benign according to our data. Variant chr7-157009949-AGCGGCG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 591761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0016 (208/129768) while in subpopulation NFE AF = 0.00207 (125/60510). AF 95% confidence interval is 0.00177. There are 0 homozygotes in GnomAd4. There are 80 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

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.396_401delCGCCGC	p.Ala133_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.396_401delCGCCGC	p.Ala133_Ala134del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000252971.5
	MNX1-AS1	ENST00000818900.1		n.296+1928_296+1933delGGCGGC		intron	N/A
	MNX1-AS1	ENST00000818901.1		n.50+843_50+848delGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 208 AN: 129760 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000571

Gnomad AMI AF: 0.0664

Gnomad AMR AF: 0.000223

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000480

Gnomad SAS AF: 0.00157

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.000556

GnomAD4 exome AF: 0.00183 AC: 1423 AN: 778358 Hom.: 4 AF XY: 0.00184 AC XY: 670 AN XY: 363640

African (AFR) AF: 0.000270 AC: 4 AN: 14816

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4990

East Asian (EAS) AF: 0.00 AC: 0 AN: 4308

South Asian (SAS) AF: 0.00173 AC: 28 AN: 16176

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

Middle Eastern (MID) AF: 0.00126 AC: 2 AN: 1586

European-Non Finnish (NFE) AF: 0.00187 AC: 1327 AN: 707852

Other (OTH) AF: 0.00235 AC: 61 AN: 25944

GnomAD4 genome AF: 0.00160 AC: 208 AN: 129768 Hom.: 0 Cov.: 0 AF XY: 0.00127 AC XY: 80 AN XY: 62920

African (AFR) AF: 0.000570 AC: 20 AN: 35094

American (AMR) AF: 0.000222 AC: 3 AN: 13498

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

East Asian (EAS) AF: 0.000482 AC: 2 AN: 4146

South Asian (SAS) AF: 0.00157 AC: 6 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: 0.00207 AC: 125 AN: 60510

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, single submitter

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=193/7	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;