NM_005675.6:c.254T>C

Variant names:

• chr22-18906708-T-C
• rs367623093
• NM_005675.6:c.254T>C

Variant summary

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

The NM_005675.6(DGCR6):​c.254T>C​(p.Leu85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L85Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 0)
• Consequence: DGCR6 NM_005675.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.08
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005675.6. 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
	DGCR6	NM_005675.6	MANE Select	c.254T>C	p.Leu85Pro	missense	Exon 2 of 5	NP_005666.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DGCR6	ENST00000331444.12	TSL:1 MANE Select	c.254T>C	p.Leu85Pro	missense	Exon 2 of 5	ENSP00000331681.6	Q14129-1
	ENSG00000283809	ENST00000638240.1	TSL:5	c.254T>C	p.Leu85Pro	missense	Exon 2 of 6	ENSP00000492446.1	A0A1W2PRQ8
	DGCR6	ENST00000413981.5	TSL:1	c.-155T>C		5_prime_UTR	Exon 2 of 5	ENSP00000402409.1	Q6FGH4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.000113 AC: 28 AN: 247504 AF XY: 0.000141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000496

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.000235 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000660 AC: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.91
MVP		0.64
MPC		0.62
ClinPred		0.85	D
GERP RS		4.0
PromoterAI		-0.12	Neutral
Varity_R		0.94
gMVP		0.86
Mutation Taster		=224/76	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: rs367623093; hg19: chr22-18894221;