1-53459752-C-T

Variant names:

• chr1-53459752-C-T
• rs916468382
• NM_033067.3:c.299C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033067.3(DMRTB1):​c.299C>T​(p.Pro100Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,211,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. P100R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: DMRTB1 NM_033067.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10159308).

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.299C>T	p.Pro100Leu	missense	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.299C>T	p.Pro100Leu	missense	Exon 1 of 4	ENSP00000360500.3	Q96MA1
	DMRTB1	ENST00000463126.1	TSL:5	n.-224C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000743 AC: 9 AN: 1211262 Hom.: 0 Cov.: 31 AF XY: 0.00000676 AC XY: 4 AN XY: 592062

African (AFR) AF: 0.0000442 AC: 1 AN: 22642

American (AMR) AF: 0.00 AC: 0 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16314

East Asian (EAS) AF: 0.00 AC: 0 AN: 24126

South Asian (SAS) AF: 0.00 AC: 0 AN: 56838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3328

European-Non Finnish (NFE) AF: 0.00000806 AC: 8 AN: 993094

Other (OTH) AF: 0.00 AC: 0 AN: 48422

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.1
DANN	Uncertain	0.98
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.055
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		0.47	P
Vest4		0.051
MutPred		0.29		Gain of catalytic residue at P100 (P = 0.0435)
MVP		0.043
MPC		0.47
ClinPred		0.59	D
GERP RS		1.3
PromoterAI		-0.037	Neutral
Varity_R		0.053
gMVP		0.10
Mutation Taster		=92/8	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: rs916468382; hg19: chr1-53925425; COSMIC: COSV65113452; COSMIC: COSV65113452;