22-23626033-C-G

Variant names:

• chr22-23626033-C-G
• rs750800958
• NM_016449.4:c.224G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016449.4(DRICH1):​c.224G>C​(p.Arg75Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRICH1 NM_016449.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06047374).

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.224G>C	p.Arg75Pro	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.224G>C	p.Arg75Pro	missense	Exon 2 of 12	ENSP00000316137.5	Q6PGQ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.3
DANN	Benign	0.59
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.27
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.0090
Sift	Benign	0.15	T
Sift4G	Benign	0.27	T
Polyphen		0.34	B
Vest4		0.17
MutPred		0.22		Gain of loop (P = 0.024)
MVP		0.12
MPC		0.30
ClinPred		0.10	T
GERP RS		0.40
Varity_R		0.14
gMVP		0.077
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: rs750800958; hg19: chr22-23968220;