NM_005675.6:c.362G>T

Variant names:

• chr22-18910262-G-T
• rs552431444
• NM_005675.6:c.362G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005675.6(DGCR6):​c.362G>T​(p.Arg121Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102

Genes affected

DGCR6 (HGNC:2846): (DiGeorge syndrome critical region gene 6) DiGeorge syndrome, and more widely, the CATCH 22 syndrome, are associated with microdeletions in chromosomal region 22q11.2. The product of this gene shares homology with the Drosophila melanogaster gonadal protein, which participates in gonadal and germ cell development, and with the gamma-1 subunit of human laminin. This gene is a candidate for involvement in DiGeorge syndrome pathology and in schizophrenia. [provided by RefSeq, Nov 2008]

ENSG00000283809 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.182248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DGCR6	NM_005675.6	c.362G>T	p.Arg121Leu	missense_variant	Exon 3 of 5	ENST00000331444.12	NP_005666.2
DGCR6	XM_047441509.1	c.481G>T	p.Glu161*	stop_gained	Exon 4 of 4		XP_047297465.1
DGCR6	XM_047441510.1	c.155G>T	p.Arg52Leu	missense_variant	Exon 3 of 5		XP_047297466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DGCR6	ENST00000331444.12	c.362G>T	p.Arg121Leu	missense_variant	Exon 3 of 5	1	NM_005675.6	ENSP00000331681.6
ENSG00000283809	ENST00000638240.1	c.362G>T	p.Arg121Leu	missense_variant	Exon 3 of 6	5		ENSP00000492446.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Benign	0.035	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.076
Sift	Benign	0.071	T;.
Sift4G	Benign	0.36	T;.
Polyphen		0.32	B;.
Vest4		0.31
MutPred		0.55		Loss of MoRF binding (P = 0.1714);Loss of MoRF binding (P = 0.1714);
MVP		0.42
MPC		0.17
ClinPred		0.30	T
GERP RS		2.6
Varity_R		0.054
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs552431444; hg19: chr22-18897775;