5-119071605-C-T

Variant names:

• chr5-119071605-C-T
• rs138845349
• NM_001290321.3:c.36C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001290321.3(DMXL1):​c.36C>T​(p.Asn12Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000852 in 1,605,250 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (6 hom.)
• Consequence: DMXL1 NM_001290321.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.975
• Publications: 0 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 5-119071605-C-T is Benign according to our data. Variant chr5-119071605-C-T is described in ClinVar as Benign. ClinVar VariationId is 776061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.975 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 gene

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.36C>T	p.Asn12Asn	synonymous	Exon 1 of 44	NP_001277250.1	F5H269
	DMXL1	NM_001349239.2		c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 45	NP_001336168.1	F5H269
	DMXL1	NM_001349240.2		c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 44	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.36C>T	p.Asn12Asn	synonymous	Exon 1 of 44	ENSP00000439479.1	F5H269
	DMXL1	ENST00000311085.8	TSL:1	c.36C>T	p.Asn12Asn	synonymous	Exon 1 of 43	ENSP00000309690.8	Q9Y485
	DMXL1	ENST00000503802.5	TSL:1	c.36C>T	p.Asn12Asn	synonymous	Exon 2 of 13	ENSP00000427692.1	E7EMZ0

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152136 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000950 AC: 219 AN: 230534 AF XY: 0.000761

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000541

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000243

Gnomad OTH exome AF: 0.000532

GnomAD4 exome AF: 0.000572 AC: 831 AN: 1452996 Hom.: 6 Cov.: 31 AF XY: 0.000468 AC XY: 338 AN XY: 721828

African (AFR) AF: 0.0147 AC: 486 AN: 33150

American (AMR) AF: 0.000683 AC: 30 AN: 43906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25864

East Asian (EAS) AF: 0.00 AC: 0 AN: 39270

South Asian (SAS) AF: 0.0000594 AC: 5 AN: 84204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.000228 AC: 253 AN: 1108346

Other (OTH) AF: 0.000949 AC: 57 AN: 60054

GnomAD4 genome AF: 0.00352 AC: 536 AN: 152254 Hom.: 4 Cov.: 32 AF XY: 0.00324 AC XY: 241 AN XY: 74428

African (AFR) AF: 0.0120 AC: 499 AN: 41558

American (AMR) AF: 0.00157 AC: 24 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00208 Hom.: 1

Bravo AF: 0.00431

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DMXL1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.95
PhyloP100		0.97
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs138845349; hg19: chr5-118407300;