NM_001371762.2:c.185C>G

Variant names:

• chr1-158181578-C-G
• NM_001371762.2:c.185C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001371762.2(CD1D):​c.185C>G​(p.Ser62Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S62L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD1D NM_001371762.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 0 publications found

Genes affected

CD1D (HGNC:1637): (CD1d molecule) This gene encodes a divergent member of the CD1 family of transmembrane glycoproteins, which are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. The CD1 proteins mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. The protein encoded by this gene localizes to late endosomes and lysosomes via a tyrosine-based motif in the cytoplasmic tail. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

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_001371762.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	NM_001371762.2	MANE Select	c.185C>G	p.Ser62Trp	missense	Exon 2 of 6	NP_001358691.1	P15813
	CD1D	NM_001371761.1		c.-128C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001358690.1	A0A669KAZ2
	CD1D	NM_001371763.1		c.185C>G	p.Ser62Trp	missense	Exon 3 of 7	NP_001358692.1	P15813

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD1D	ENST00000674085.2	MANE Select	c.185C>G	p.Ser62Trp	missense	Exon 2 of 6	ENSP00000501100.1	P15813
	CD1D	ENST00000368171.5	TSL:1	c.185C>G	p.Ser62Trp	missense	Exon 3 of 7	ENSP00000357153.3	P15813
	CD1D	ENST00000673701.2		c.-128C>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000501010.1	A0A669KAZ2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Benign	0.081
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0082	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		2.1
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.098
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.46
MutPred		0.41		Loss of disorder (P = 0.0024)
MVP		0.54
MPC		0.77
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.37
gMVP		0.62
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

hg19: chr1-158151368;