NM_033067.3:c.364C>T

Variant names:

• chr1-53459817-C-T
• rs765450052
• NM_033067.3:c.364C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033067.3(DMRTB1):​c.364C>T​(p.Gln122*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,293,578 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: DMRTB1 NM_033067.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275
• Publications: 0 publications found

Genes affected

DMRTB1 (HGNC:13913): (DMRT like family B with proline rich C-terminal 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033067.3. 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
	DMRTB1	NM_033067.3	MANE Select	c.364C>T	p.Gln122*	stop_gained	Exon 1 of 4	NP_149056.1	Q96MA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTB1	ENST00000371445.3	TSL:1 MANE Select	c.364C>T	p.Gln122*	stop_gained	Exon 1 of 4	ENSP00000360500.3	Q96MA1
	DMRTB1	ENST00000463126.1	TSL:5	n.-159C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1293578 Hom.: 0 Cov.: 31 AF XY: 0.00000157 AC XY: 1 AN XY: 636688

⚠️ 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: 25054

American (AMR) AF: 0.00 AC: 0 AN: 21230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21780

East Asian (EAS) AF: 0.00 AC: 0 AN: 26960

South Asian (SAS) AF: 0.00 AC: 0 AN: 70380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3798

European-Non Finnish (NFE) AF: 9.63e-7 AC: 1 AN: 1038834

Other (OTH) AF: 0.00 AC: 0 AN: 53012

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Uncertain	0.98
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.055	N
PhyloP100		0.28
Vest4		0.065
GERP RS		-2.9
PromoterAI		0.0075	Neutral
Mutation Taster		=79/121	disease causing (fs/PTC)

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: rs765450052; hg19: chr1-53925490;