chr22-23626037-C-G

Variant names:

• chr22-23626037-C-G
• rs1928043107
• NM_016449.4:c.220G>C

Variant summary

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

The NM_016449.4(DRICH1):​c.220G>C​(p.Asp74His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000014 (0 hom.)
• Consequence: DRICH1 NM_016449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.267
• Publications: 0 publications found

Genes affected

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

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=0.071235836).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016449.4. 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
	DRICH1	NM_016449.4	MANE Select	c.220G>C	p.Asp74His	missense	Exon 2 of 12	NP_057533.2	Q6PGQ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRICH1	ENST00000317749.9	TSL:1 MANE Select	c.220G>C	p.Asp74His	missense	Exon 2 of 12	ENSP00000316137.5	Q6PGQ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460540 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726628

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000449 AC: 2 AN: 44544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39650

South Asian (SAS) AF: 0.00 AC: 0 AN: 86000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111242

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	11
DANN	Benign	0.41
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.27
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.045
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.016	D
Polyphen		0.62	P
Vest4		0.34
MutPred		0.29		Gain of sheet (P = 0.0477)
MVP		0.072
MPC		0.26
ClinPred		0.13	T
GERP RS		-1.6
Varity_R		0.080
gMVP		0.055
Mutation Taster		=99/1	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: rs1928043107; hg19: chr22-23968224;