rs145455346

Variant names:

• chr19-41850346-C-T
• rs145455346
• NM_001040283.3:c.790C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-41850346-C-T
• chr19-41850346-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040283.3(DMRTC2):​c.790C>T​(p.Pro264Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,519,744 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: DMRTC2 NM_001040283.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40
• Publications: 1 publications found

Genes affected

DMRTC2 (HGNC:13911): (DMRT like family C2) 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 gamete generation and positive regulation of histone H3-K9 methylation. Predicted to be located in XY body. 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0587458).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040283.3. 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
	DMRTC2	NM_001040283.3	MANE Select	c.790C>T	p.Pro264Ser	missense	Exon 7 of 9	NP_001035373.1	Q8IXT2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMRTC2	ENST00000269945.8	TSL:1 MANE Select	c.790C>T	p.Pro264Ser	missense	Exon 7 of 9	ENSP00000269945.2	Q8IXT2-1
	DMRTC2	ENST00000596827.5	TSL:2	c.790C>T	p.Pro264Ser	missense	Exon 7 of 8	ENSP00000469525.1	B4DX56
	DMRTC2	ENST00000599022.1	TSL:3	n.103C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000282 AC: 5 AN: 177560 AF XY: 0.0000107

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000249

GnomAD4 exome AF: 0.00000585 AC: 8 AN: 1367598 Hom.: 0 Cov.: 31 AF XY: 0.00000447 AC XY: 3 AN XY: 670782

African (AFR) AF: 0.00 AC: 0 AN: 30014

American (AMR) AF: 0.000169 AC: 5 AN: 29650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20036

East Asian (EAS) AF: 0.00 AC: 0 AN: 38380

South Asian (SAS) AF: 0.00 AC: 0 AN: 70294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5314

European-Non Finnish (NFE) AF: 0.00000281 AC: 3 AN: 1067568

Other (OTH) AF: 0.00 AC: 0 AN: 56280

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00105 AC: 16 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

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	0.076
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.050
Eigen_PC	Benign	0.0082
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.054
Sift	Benign	0.032	D
Sift4G	Uncertain	0.048	D
Polyphen		1.0	D
Vest4		0.22
MutPred		0.16		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.082
MPC		0.19
ClinPred		0.25	T
GERP RS		3.8
Varity_R		0.045
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs145455346; hg19: chr19-42354414;