chr1-53459735-C-A

Variant names:

• chr1-53459735-C-A
• NM_033067.3:c.282C>A

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.282C>A​(p.Ser94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,204,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: DMRTB1 NM_033067.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• 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=0.10334277).

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.282C>A	p.Ser94Arg	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.282C>A	p.Ser94Arg	missense	Exon 1 of 4	ENSP00000360500.3	Q96MA1
	DMRTB1	ENST00000463126.1	TSL:5	n.-241C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1204492 Hom.: 0 Cov.: 31 AF XY: 0.00000170 AC XY: 1 AN XY: 587670

African (AFR) AF: 0.00 AC: 0 AN: 22442

American (AMR) AF: 0.00 AC: 0 AN: 9452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15584

East Asian (EAS) AF: 0.00 AC: 0 AN: 24450

South Asian (SAS) AF: 0.00 AC: 0 AN: 53998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 989676

Other (OTH) AF: 0.0000208 AC: 1 AN: 48104

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.084
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.18	T
Polyphen		0.062	B
Vest4		0.17
MutPred		0.26		Loss of glycosylation at S94 (P = 0.0022)
MVP		0.068
MPC		0.82
ClinPred		0.44	T
GERP RS		1.3
PromoterAI		0.24	Neutral
Varity_R		0.16
gMVP		0.14
Mutation Taster		=95/5	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

hg19: chr1-53925408;