5-119196339-A-T

Variant names:

• chr5-119196339-A-T
• rs6595178
• NM_001290321.3:c.7458-32A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290321.3(DMXL1):​c.7458-32A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,392,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DMXL1 NM_001290321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 13 publications found

Genes affected

DMXL1 (HGNC:2937): (Dmx like 1) The protein encoded by this gene is a member of the WD repeat superfamily of proteins, which have regulatory functions. This gene is expressed in many tissue types including several types of eye tissue, and it has been associated with ocular phenotypes. In addition, it is upregulated in cultured cells that overexpress growth factor independence 1B, a transcription factor that is essential for hematopoietic cell development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290321.3. 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
	DMXL1	NM_001290321.3	MANE Select	c.7458-32A>T		intron	N/A	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.7458-32A>T		intron	N/A	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.7458-32A>T		intron	N/A	NP_001336169.1	Q9Y485

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMXL1	ENST00000539542.6	TSL:1 MANE Select	c.7458-32A>T		intron	N/A	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.7458-32A>T		intron	N/A	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000939842.1		c.6060-32A>T		intron	N/A	ENSP00000609901.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1392808 Hom.: 0 Cov.: 22 AF XY: 0.00000143 AC XY: 1 AN XY: 697076

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32174

American (AMR) AF: 0.00 AC: 0 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25648

East Asian (EAS) AF: 0.0000508 AC: 2 AN: 39342

South Asian (SAS) AF: 0.00 AC: 0 AN: 84906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1049078

Other (OTH) AF: 0.00 AC: 0 AN: 58070

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 84673

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.19
PhyloP100		-0.94

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: rs6595178;

hg19: chr5-118532034;