1-117010116-G-A

Variant summary

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

The NM_001256106.3(CD101):c.310G>A(p.Val104Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 33)
• Consequence: CD101 NM_001256106.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.46

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]

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=0.23678675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD101	NM_001256106.3	c.310G>A	p.Val104Ile	missense_variant	2/10	ENST00000682167.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD101	ENST00000682167.1	c.310G>A	p.Val104Ile	missense_variant	2/10		NM_001256106.3	P1
CD101	ENST00000369470.1	c.310G>A	p.Val104Ile	missense_variant	2/10	1		P1
CD101	ENST00000256652.8	c.310G>A	p.Val104Ile	missense_variant	2/9	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251178 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135728

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.310G>A (p.V104I) alteration is located in exon 2 (coding exon 2) of the CD101 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the valine (V) at amino acid position 104 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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.014
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T;.
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	0.96	D;D
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.28
Sift	Benign	0.097	T;T
Sift4G	Uncertain	0.012	D;D
Polyphen		0.23	B;B
Vest4		0.12
MutPred		0.67		Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);
MVP		0.71
MPC		0.39
ClinPred		0.62	D
GERP RS		4.9
Varity_R		0.078
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

LitVar

Other links and lift over

dbSNP: rs945577895; hg19: chr1-117552738;