22-23613650-C-T

Position:

• chr22-23613650-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016449.4(DRICH1):​c.632G>A​(p.Arg211Gln) 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 1,452,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: DRICH1 NM_016449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.238

Genes affected

DRICH1 (HGNC:28031): (aspartate rich 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DRICH1	NM_016449.4	c.632G>A	p.Arg211Gln	missense_variant	10/12	ENST00000317749.9	NP_057533.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRICH1	ENST00000317749.9	c.632G>A	p.Arg211Gln	missense_variant	10/12	1	NM_016449.4	ENSP00000316137.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000363 AC: 9 AN: 247622 Hom.: 0 AF XY: 0.0000669 AC XY: 9 AN XY: 134526

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1452104 Hom.: 0 Cov.: 28 AF XY: 0.0000194 AC XY: 14 AN XY: 723078

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000815

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000127

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 08, 2022

The c.632G>A (p.R211Q) alteration is located in exon 10 (coding exon 10) of the DRICH1 gene. This alteration results from a G to A substitution at nucleotide position 632, causing the arginine (R) at amino acid position 211 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	4.8
DANN	Benign	0.70
DEOGEN2	Benign	0.0042	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.42	.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N;N
PROVEAN	Benign	0.060	N;.
REVEL	Benign	0.010
Sift	Benign	0.48	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.0060	B;B
Vest4		0.046
MutPred		0.33		Loss of phosphorylation at S214 (P = 0.0913);Loss of phosphorylation at S214 (P = 0.0913);
MVP		0.076
MPC		0.14
ClinPred		0.0065	T
GERP RS		-1.8
Varity_R		0.020
gMVP		0.0016

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.39		Position offset: 10

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

Publications

LitVar

Other links and lift over

dbSNP: rs750442552; hg19: chr22-23955837;