chr1-53459715-G-A

Variant names:

• chr1-53459715-G-A
• rs1644007398
• NM_033067.3:c.262G>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.262G>A​(p.Val88Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000072 in 1,249,584 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V88L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: DMRTB1 NM_033067.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472
• 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: 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=0.049023896).

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.262G>A	p.Val88Ile	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.262G>A	p.Val88Ile	missense	Exon 1 of 4	ENSP00000360500.3	Q96MA1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000720 AC: 9 AN: 1249584 Hom.: 0 Cov.: 31 AF XY: 0.00000654 AC XY: 4 AN XY: 611774

African (AFR) AF: 0.00 AC: 0 AN: 23188

American (AMR) AF: 0.00 AC: 0 AN: 11884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17844

East Asian (EAS) AF: 0.00 AC: 0 AN: 26814

South Asian (SAS) AF: 0.0000168 AC: 1 AN: 59522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3482

European-Non Finnish (NFE) AF: 0.00000789 AC: 8 AN: 1014170

Other (OTH) AF: 0.00 AC: 0 AN: 50484

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.096
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.3
DANN	Benign	0.79
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.47
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.058
Sift	Benign	0.33	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.12		Loss of sheet (P = 0.1158)
MVP		0.068
MPC		0.37
ClinPred		0.18	T
GERP RS		-2.3
PromoterAI		0.042	Neutral
Varity_R		0.034
gMVP		0.087
Mutation Taster		=89/11	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: rs1644007398; hg19: chr1-53925388;