chr9-22447195-C-T

Variant names:

• chr9-22447195-C-T
• NM_022160.3:c.130C>T

Variant summary

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

The NM_022160.3(DMRTA1):​c.130C>T​(p.Pro44Ser) 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. 15/22 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)
• Consequence: DMRTA1 NM_022160.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.734
• Publications: 0 publications found

Genes affected

DMRTA1 (HGNC:13826): (DMRT like family A1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in germ cell development; regulation of transcription by RNA polymerase II; and sex differentiation. Predicted to act upstream of or within male mating behavior and ovarian follicle development. 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=0.10597286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022160.3. 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
	DMRTA1	NM_022160.3	MANE Select	c.130C>T	p.Pro44Ser	missense	Exon 1 of 2	NP_071443.2	Q5VZB9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTA1	ENST00000325870.3	TSL:1 MANE Select	c.130C>T	p.Pro44Ser	missense	Exon 1 of 2	ENSP00000319651.1	Q5VZB9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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	0.091
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.099	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.73
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.030
Sift	Benign	0.22	T
Sift4G	Benign	0.25	T
Polyphen		0.35	B
Vest4		0.15
MutPred		0.20		Loss of catalytic residue at P44 (P = 0.0054)
MVP		0.33
MPC		0.16
ClinPred		0.25	T
GERP RS		3.7
PromoterAI		-0.034	Neutral
Varity_R		0.029
gMVP		0.38
Mutation Taster		=90/10	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: chr9-22447194;