Variant chr22-23613656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_016449.4(DRICH1):c.626C>T(p.Thr209Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000874 in 1,601,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

DRICH1
NM_016449.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.672

Variant links:

Genes affected

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

DRICH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.626C>T	p.Thr209Ile	missense_variant	10/12	ENST00000317749.9	NP_057533.2	Q6PGQ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DRICH1	ENST00000317749.9 linkuse as main transcript	c.626C>T	p.Thr209Ile	missense_variant	10/12	1	NM_016449.4	ENSP00000316137.5		Q6PGQ1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000808

AC:

AN:

247542

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134452

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000345

AC:

AN:

1448874

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721698

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2024

The c.626C>T (p.T209I) alteration is located in exon 10 (coding exon 10) of the DRICH1 gene. This alteration results from a C to T substitution at nucleotide position 626, causing the threonine (T) at amino acid position 209 to be replaced by an isoleucine (I). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.2

DANN

Benign

0.68

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.24

.;T

M_CAP

Benign

0.00076

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

N;N

PROVEAN

Benign

-0.94

N;.

REVEL

Benign

0.22

Sift

Benign

0.092

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.99

D;D

Vest4

0.17

MutPred

0.24

Loss of glycosylation at T209 (P = 0.0337);Loss of glycosylation at T209 (P = 0.0337);

MVP

0.048

MPC

0.34

ClinPred

0.059

GERP RS

-1.5

Varity_R

0.028

gMVP

0.0054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.38

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.38

Position offset: 4

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over