7-157009949-AGCGGCGGCGGCGGCGGCG-AGCGGCGGCGGCGGCG

Variant names:

• chr7-157009949-AGCG-A
• rs548755417
• NM_005515.4:c.399_401delCGC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_005515.4(MNX1):​c.399_401delCGC​(p.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 0.00241 in 907,654 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (5 hom.)
• Consequence: MNX1 NM_005515.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:3
• Conservation: PhyloP100: 2.45
• 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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005515.4
• BP6: Variant 7-157009949-AGCG-A is Benign according to our data. Variant chr7-157009949-AGCG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 591750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00227 (294/129770) while in subpopulation SAS AF = 0.00603 (23/3814). AF 95% confidence interval is 0.00412. There are 2 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,AD 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	NM_005515.4	MANE Select	c.399_401delCGC	p.Ala134del	disruptive_inframe_deletion	Exon 1 of 3	NP_005506.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MNX1	ENST00000252971.11	TSL:1 MANE Select	c.399_401delCGC	p.Ala134del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000252971.5	P50219-1
	MNX1-AS1	ENST00000818900.1		n.296+1931_296+1933delGGC		intron	N/A
	MNX1-AS1	ENST00000818901.1		n.50+846_50+848delGGC		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 294 AN: 129762 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00245

Gnomad ASJ AF: 0.0103

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.00602

Gnomad FIN AF: 0.000897

Gnomad MID AF: 0.00403

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.00445

GnomAD4 exome AF: 0.00243 AC: 1894 AN: 777884 Hom.: 5 AF XY: 0.00244 AC XY: 887 AN XY: 363418

African (AFR) AF: 0.00149 AC: 22 AN: 14814

American (AMR) AF: 0.000746 AC: 1 AN: 1340

Ashkenazi Jewish (ASJ) AF: 0.00641 AC: 32 AN: 4990

East Asian (EAS) AF: 0.00349 AC: 15 AN: 4300

South Asian (SAS) AF: 0.00520 AC: 84 AN: 16154

European-Finnish (FIN) AF: 0.00149 AC: 2 AN: 1340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1584

European-Non Finnish (NFE) AF: 0.00238 AC: 1683 AN: 707438

Other (OTH) AF: 0.00212 AC: 55 AN: 25924

GnomAD4 genome AF: 0.00227 AC: 294 AN: 129770 Hom.: 2 Cov.: 0 AF XY: 0.00243 AC XY: 153 AN XY: 62920

African (AFR) AF: 0.00162 AC: 57 AN: 35090

American (AMR) AF: 0.00244 AC: 33 AN: 13498

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 33 AN: 3214

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

South Asian (SAS) AF: 0.00603 AC: 23 AN: 3814

European-Finnish (FIN) AF: 0.000897 AC: 6 AN: 6688

Middle Eastern (MID) AF: 0.00435 AC: 1 AN: 230

European-Non Finnish (NFE) AF: 0.00207 AC: 125 AN: 60514

Other (OTH) AF: 0.00443 AC: 8 AN: 1806

Alfa AF: 0.00132 Hom.: 1464

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	2	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=84/16	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs548755417; hg19: chr7-156802643;