Genetic Variant NM_001256106.3:c.2647C>A (chr1-117025727-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/24 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. H883Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.154

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256106.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD101	NM_001256106.3	MANE Select	c.2647C>A	p.His883Asn	missense	Exon 8 of 10	NP_001243035.1	Q93033
CD101	NM_001256109.3		c.2647C>A	p.His883Asn	missense	Exon 8 of 10	NP_001243038.1	Q93033
CD101	NM_004258.6		c.2647C>A	p.His883Asn	missense	Exon 8 of 10	NP_004249.2	Q93033

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD101	ENST00000682167.1	MANE Select	c.2647C>A	p.His883Asn	missense	Exon 8 of 10	ENSP00000508039.1	Q93033
CD101	ENST00000369470.1	TSL:1	c.2647C>A	p.His883Asn	missense	Exon 8 of 10	ENSP00000358482.1	Q93033
CD101	ENST00000256652.8	TSL:2	c.2647C>A	p.His883Asn	missense	Exon 8 of 9	ENSP00000256652.4	Q93033

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251402

AF XY:

0.0000147

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.0000166

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.18

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.62

M_CAP

Benign

0.024

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

0.15

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.071

Sift

Uncertain

0.015

Sift4G

Benign

0.061

Polyphen

0.67

Vest4

0.24

MutPred

0.31

Gain of relative solvent accessibility (P = 0.0522)

MVP

0.78

MPC

0.13

ClinPred

0.58

GERP RS

3.4

Varity_R

0.21

gMVP

0.19

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over