NM_032110.3:c.1107T>A

Variant names:

• chr1-50419187-A-T
• NM_032110.3:c.1107T>A

Variant summary

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

The NM_032110.3(DMRTA2):​c.1107T>A​(p.Asp369Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DMRTA2 NM_032110.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.577
• Publications: 0 publications found

Genes affected

DMRTA2 (HGNC:13908): (DMRT like family A2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II and sex differentiation. Predicted to act upstream of or within nervous system development and skeletal muscle cell differentiation. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAF1-AS1 (HGNC:40228): (FAF1 antisense RNA 1)

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=0.049287528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032110.3. 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
	DMRTA2	NM_032110.3	MANE Select	c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	NP_115486.1	Q96SC8
	DMRTA2	NM_001437821.1		c.1107T>A	p.Asp369Glu	missense	Exon 2 of 2	NP_001424750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTA2	ENST00000404795.4	TSL:5 MANE Select	c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	ENSP00000383909.3	Q96SC8
	DMRTA2	ENST00000418121.5	TSL:1	c.1107T>A	p.Asp369Glu	missense	Exon 2 of 2	ENSP00000399370.1	Q96SC8
	DMRTA2	ENST00000948348.1		c.1107T>A	p.Asp369Glu	missense	Exon 3 of 3	ENSP00000618407.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1175526 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 569578

African (AFR) AF: 0.00 AC: 0 AN: 23752

American (AMR) AF: 0.00 AC: 0 AN: 10756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14844

East Asian (EAS) AF: 0.00 AC: 0 AN: 25518

South Asian (SAS) AF: 0.00 AC: 0 AN: 51190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 974122

Other (OTH) AF: 0.00 AC: 0 AN: 46930

GnomAD4 genome Cov.: 33

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	0.073
PhyloP100		-0.58
Varity_R		0.043
gMVP		0.18
Mutation Taster		=96/4	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-50884859;