Genetic Variant CD101:p.Gly877Trp (chr1-117025709-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001256106.3(CD101):c.2629G>T(p.Gly877Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 0.000016 ( 0 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150

Variant links:

Genes affected

CD101 (HGNC:5949): (CD101 molecule) Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CD101 links:

CD101-AS1 (HGNC:55665): (CD101 antisense RNA 1)

CD101-AS1 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 rank	MANE	Protein	UniProt
CD101	NM_001256106.3 link	c.2629G>T	p.Gly877Trp	missense_variant	Exon 8 of 10	ENST00000682167.1	NP_001243035.1	Q93033

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD101	ENST00000682167.1 link	c.2629G>T	p.Gly877Trp	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1	Q93033
CD101	ENST00000369470.1 link	c.2629G>T	p.Gly877Trp	missense_variant	Exon 8 of 10	1		ENSP00000358482.1	Q93033
CD101	ENST00000256652.8 link	c.2629G>T	p.Gly877Trp	missense_variant	Exon 8 of 9	2		ENSP00000256652.4	Q93033
CD101-AS1	ENST00000445523.1 link	n.1587C>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251330

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000172

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2629G>T (p.G877W) alteration is located in exon 8 (coding exon 8) of the CD101 gene. This alteration results from a G to T substitution at nucleotide position 2629, causing the glycine (G) at amino acid position 877 to be replaced by a tryptophan (W). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.33

T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.68

T;.

M_CAP

Benign

0.083

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.44

MutPred

0.64

Loss of disorder (P = 0.0039);Loss of disorder (P = 0.0039);

MVP

0.60

MPC

0.47

ClinPred

0.97

GERP RS

-1.1

Varity_R

0.32

gMVP

0.43

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

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