9-989943-T-G

Variant names:

• chr9-989943-T-G
• rs6477419
• NM_021240.4:c.455-98T>G

Variant summary

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

The NM_021240.4(DMRT3):​c.455-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,010 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: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: DMRT3 NM_021240.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 4 publications found

Genes affected

DMRT3 (HGNC:13909): (doublesex and mab-3 related transcription factor 3) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in male sex differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult walking behavior; transmission of nerve impulse; and ventral spinal cord interneuron specification. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000294527 (HGNC:):

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=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRT3	NM_021240.4	c.455-98T>G		intron_variant	Intron 1 of 1	ENST00000190165.3	NP_067063.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRT3	ENST00000190165.3	c.455-98T>G		intron_variant	Intron 1 of 1	1	NM_021240.4	ENSP00000190165.2
DMRT3	ENST00000417254.1	c.-55T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 1	6		ENSP00000387472.1
DMRT3	ENST00000417254.1	c.-55T>G		5_prime_UTR_variant	Exon 1 of 1	6		ENSP00000387472.1
ENSG00000294527	ENST00000724117.1	n.422-3917A>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1330010 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 655280

African (AFR) AF: 0.00 AC: 0 AN: 29404

American (AMR) AF: 0.00 AC: 0 AN: 29866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20072

East Asian (EAS) AF: 0.00 AC: 0 AN: 38694

South Asian (SAS) AF: 0.00 AC: 0 AN: 68970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5282

European-Non Finnish (NFE) AF: 9.68e-7 AC: 1 AN: 1033312

Other (OTH) AF: 0.00 AC: 0 AN: 55114

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		0.025
PromoterAI		0.0048	Neutral

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: rs6477419; hg19: chr9-989943;