NM_001256106.3:c.2647C>A

Variant summary

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

The NM_001256106.3(CD101):​c.2647C>A​(p.His883Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,888 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 (★). Synonymous variant affecting the same amino acid position (i.e. H883H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.154
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-AS1 (HGNC:55665): (CD101 antisense RNA 1)

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
CD101NM_001256106.3 linkc.2647C>A p.His883Asn missense_variant Exon 8 of 10 ENST00000682167.1 NP_001243035.1 Q93033

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD101ENST00000682167.1 linkc.2647C>A p.His883Asn missense_variant Exon 8 of 10 NM_001256106.3 ENSP00000508039.1 Q93033
CD101ENST00000369470.1 linkc.2647C>A p.His883Asn missense_variant Exon 8 of 10 1 ENSP00000358482.1 Q93033
CD101ENST00000256652.8 linkc.2647C>A p.His883Asn missense_variant Exon 8 of 9 2 ENSP00000256652.4 Q93033
CD101-AS1ENST00000445523.1 linkn.1569G>T non_coding_transcript_exon_variant Exon 4 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251402
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
0.00000410
AC:
6
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
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:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2647C>A (p.H883N) alteration is located in exon 8 (coding exon 8) of the CD101 gene. This alteration results from a C to A substitution at nucleotide position 2647, causing the histidine (H) at amino acid position 883 to be replaced by an asparagine (N). 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
0.094
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Benign
0.96
DEOGEN2
Benign
0.18
T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.62
T;.
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.071
Sift
Uncertain
0.015
D;D
Sift4G
Benign
0.061
T;T
Polyphen
0.67
P;P
Vest4
0.24
MutPred
0.31
Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP
0.78
MPC
0.13
ClinPred
0.58
D
GERP RS
3.4
Varity_R
0.21
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.28
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.28
Position offset: 25

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.

Other links and lift over

dbSNP: rs779120171; hg19: chr1-117568349; API