NM_016449.4:c.374A>C

Variant names:

• chr22-23622101-T-G
• rs773542398
• NM_016449.4:c.374A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016449.4(DRICH1):​c.374A>C​(p.Asp125Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,544,126 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.0022 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: DRICH1 NM_016449.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.189
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0163849).

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.374A>C	p.Asp125Ala	missense	Exon 4 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.374A>C	p.Asp125Ala	missense	Exon 4 of 12	ENSP00000316137.5	Q6PGQ1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 331 AN: 152040 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00766

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.0000259 AC: 6 AN: 232098 AF XY: 0.0000317

Gnomad AFR exome AF: 0.000408

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000203 AC: 282 AN: 1391968 Hom.: 1 Cov.: 32 AF XY: 0.000165 AC XY: 114 AN XY: 691520

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00720 AC: 229 AN: 31826

American (AMR) AF: 0.000429 AC: 18 AN: 41912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24496

East Asian (EAS) AF: 0.00 AC: 0 AN: 35958

South Asian (SAS) AF: 0.0000246 AC: 2 AN: 81234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50208

Middle Eastern (MID) AF: 0.00107 AC: 6 AN: 5586

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1063564

Other (OTH) AF: 0.000437 AC: 25 AN: 57184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00218 AC: 332 AN: 152158 Hom.: 1 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74396

African (AFR) AF: 0.00766 AC: 318 AN: 41514

American (AMR) AF: 0.000720 AC: 11 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00211 Hom.: 0

ExAC AF: 0.0000582 AC: 7

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	Benign	0.23
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.19
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.12
MVP		0.21
MPC		0.16
ClinPred		0.17	T
GERP RS		0.29
Varity_R		0.13
gMVP		0.012
Mutation Taster		=100/0	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: rs773542398; hg19: chr22-23964288;