1-117025882-G-C

Variant names:

• chr1-117025882-G-C
• NM_001256106.3:c.2802G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001256106.3(CD101):​c.2802G>C​(p.Met934Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000021 (0 hom.)
• Consequence: CD101 NM_001256106.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.471

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08665267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD101	NM_001256106.3	c.2802G>C	p.Met934Ile	missense_variant	Exon 8 of 10	ENST00000682167.1	NP_001243035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD101	ENST00000682167.1	c.2802G>C	p.Met934Ile	missense_variant	Exon 8 of 10		NM_001256106.3	ENSP00000508039.1
CD101	ENST00000369470.1	c.2802G>C	p.Met934Ile	missense_variant	Exon 8 of 10	1		ENSP00000358482.1
CD101	ENST00000256652.8	c.2802G>C	p.Met934Ile	missense_variant	Exon 8 of 9	2		ENSP00000256652.4
CD101-AS1	ENST00000445523.1	n.1414C>G		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458158 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724804

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2802G>C (p.M934I) alteration is located in exon 8 (coding exon 8) of the CD101 gene. This alteration results from a G to C substitution at nucleotide position 2802, causing the methionine (M) at amino acid position 934 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	Benign	0.22
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.7
DANN	Benign	0.58
DEOGEN2	Benign	0.072	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.60	T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.031
Sift	Benign	0.15	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.070	B;B
Vest4		0.11
MutPred		0.31		Gain of catalytic residue at L939 (P = 0.0519);Gain of catalytic residue at L939 (P = 0.0519);
MVP		0.10
MPC		0.10
ClinPred		0.058	T
GERP RS		3.3
Varity_R		0.11
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117568504;