chr1-117011711-A-G

Position:

• chr1-117011711-A-G

Variant summary

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

The NM_001256106.3(CD101):​c.586A>G​(p.Thr196Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 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)
• Consequence: CD101 NM_001256106.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD101	NM_001256106.3	c.586A>G	p.Thr196Ala	missense_variant	3/10	ENST00000682167.1	NP_001243035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD101	ENST00000682167.1	c.586A>G	p.Thr196Ala	missense_variant	3/10		NM_001256106.3	ENSP00000508039	P1
CD101	ENST00000369470.1	c.586A>G	p.Thr196Ala	missense_variant	3/10	1		ENSP00000358482	P1
CD101	ENST00000256652.8	c.586A>G	p.Thr196Ala	missense_variant	3/9	2		ENSP00000256652	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Apr 13, 2022

The c.586A>G (p.T196A) alteration is located in exon 3 (coding exon 3) of the CD101 gene. This alteration results from a A to G substitution at nucleotide position 586, causing the threonine (T) at amino acid position 196 to be replaced by an alanine (A). 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	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.45	T;.
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	0.52	D;D
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.14
Sift	Benign	0.10	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.64	P;P
Vest4		0.084
MutPred		0.20		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.71
MPC		0.10
ClinPred		0.30	T
GERP RS		4.4
Varity_R		0.15
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs374815004; hg19: chr1-117554333;