9-842049-CCG-TTA

Variant names:

• chr9-842049-CCG-TTA
• NM_021951.3:c.211_213delCCGinsTTA
• DMRT1 p.Pro71Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021951.3(DMRT1):​c.211_213delCCGinsTTA​(p.Pro71Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P71R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DMRT1 NM_021951.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.50
• Publications: 0 publications found

Genes affected

DMRT1 (HGNC:2934): (doublesex and mab-3 related transcription factor 1) This gene is found in a cluster with two other members of the gene family, having in common a zinc finger-like DNA-binding motif (DM domain). The DM domain is an ancient, conserved component of the vertebrate sex-determining pathway that is also a key regulator of male development in flies and nematodes. This gene exhibits a gonad-specific and sexually dimorphic expression pattern. Defective testicular development and XY feminization occur when this gene is hemizygous. [provided by RefSeq, Jul 2008]

DMRT1 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• 46,XX disorder of sex development

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000294371 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021951.3. 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
	DMRT1	NM_021951.3	MANE Select	c.211_213delCCGinsTTA	p.Pro71Leu	missense	N/A	NP_068770.2	Q9Y5R6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRT1	ENST00000382276.8	TSL:1 MANE Select	c.211_213delCCGinsTTA	p.Pro71Leu	missense	N/A	ENSP00000371711.3	Q9Y5R6-1
	DMRT1	ENST00000564322.1	TSL:1	n.360_362delCCGinsTTA		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000294371	ENST00000723200.1		n.401+4804_401+4806delCGGinsTAA		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.5

Splicing

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

hg19: chr9-842049;