Genetic Variant CD101:p.Ser887Leu (chr1-117025740-C-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.2660C>T(p.Ser887Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S887P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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:

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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.2660C>T	p.Ser887Leu	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.2660C>T	p.Ser887Leu	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1	Q93033
CD101	ENST00000369470.1 link	c.2660C>T	p.Ser887Leu	missense_variant	Exon 8 of 10	1		ENSP00000358482.1	Q93033
CD101	ENST00000256652.8 link	c.2660C>T	p.Ser887Leu	missense_variant	Exon 8 of 9	2		ENSP00000256652.4	Q93033
CD101-AS1	ENST00000445523.1 link	n.1556G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727244

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2660C>T (p.S887L) alteration is located in exon 8 (coding exon 8) of the CD101 gene. This alteration results from a C to T substitution at nucleotide position 2660, causing the serine (S) at amino acid position 887 to be replaced by a leucine (L). 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

0.089

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.71

T;.

M_CAP

Benign

0.032

MetaRNN

Benign

0.36

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.22

Sift

Benign

0.15

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.89

P;P

Vest4

0.31

MutPred

0.49

Loss of disorder (P = 0.0287);Loss of disorder (P = 0.0287);

MVP

0.83

MPC

0.20

ClinPred

0.53

GERP RS

3.4

Varity_R

0.074

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 12

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