1-53459722-T-A

Variant names:

• chr1-53459722-T-A
• rs1160645251
• NM_033067.3:c.269T>A

Variant summary

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

The NM_033067.3(DMRTB1):​c.269T>A​(p.Val90Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000812 in 1,231,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V90A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: DMRTB1 NM_033067.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.598

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: 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 (MetaRNN=0.06672612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMRTB1	NM_033067.3	c.269T>A	p.Val90Asp	missense_variant	Exon 1 of 4	ENST00000371445.3	NP_149056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMRTB1	ENST00000371445.3	c.269T>A	p.Val90Asp	missense_variant	Exon 1 of 4	1	NM_033067.3	ENSP00000360500.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.12e-7 AC: 1 AN: 1231208 Hom.: 0 Cov.: 31 AF XY: 0.00000166 AC XY: 1 AN XY: 602034

African (AFR) AF: 0.00 AC: 0 AN: 22822

American (AMR) AF: 0.00 AC: 0 AN: 10964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16730

East Asian (EAS) AF: 0.00 AC: 0 AN: 25938

South Asian (SAS) AF: 0.00 AC: 0 AN: 57262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3392

European-Non Finnish (NFE) AF: 9.96e-7 AC: 1 AN: 1003946

Other (OTH) AF: 0.00 AC: 0 AN: 49512

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.11
DANN	Benign	0.74
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.60
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.017
Sift	Benign	0.26	T
Sift4G	Benign	0.082	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.14		Gain of relative solvent accessibility (P = 0.0479);
MVP		0.043
MPC		0.74
ClinPred		0.26	T
GERP RS		-3.7
PromoterAI		-0.013	Neutral
Varity_R		0.14
gMVP		0.22
Mutation Taster		=93/7	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

Publications

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Other links and lift over

dbSNP: rs1160645251; hg19: chr1-53925395;