rs11230562

Variant names:

• chr11-61008714-C-G
• NM_006725.5:c.650C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-61008714-C-G
• chr11-61008714-C-T

Variant summary

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

The NM_006725.5(CD6):​c.650C>G​(p.Thr217Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T217M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CD6 NM_006725.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764

Genes affected

CD6 (HGNC:1691): (CD6 molecule) This gene encodes a protein found on the outer membrane of T-lymphocytes as well as some other immune cells. The encoded protein contains three scavenger receptor cysteine-rich (SRCR) domains and a binding site for an activated leukocyte cell adhesion molecule. The gene product is important for continuation of T cell activation. This gene may be associated with susceptibility to multiple sclerosis (PMID: 19525953, 21849685). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

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=0.25487125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD6	NM_006725.5	c.650C>G	p.Thr217Arg	missense_variant	Exon 4 of 13	ENST00000313421.11	NP_006716.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD6	ENST00000313421.11	c.650C>G	p.Thr217Arg	missense_variant	Exon 4 of 13	1	NM_006725.5	ENSP00000323280.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454298 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 722868

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T;T;.;.;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.31	T;T;T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.;.;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N;N;N;N
REVEL	Benign	0.092
Sift	Uncertain	0.013	D;D;D;D;D
Sift4G	Benign	0.062	T;D;D;D;D
Polyphen		0.88	P;.;D;P;P
Vest4		0.13
MutPred		0.59		Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);Gain of solvent accessibility (P = 0.0058);
MVP		0.52
MPC		1.8
ClinPred		0.33	T
GERP RS		0.67
Varity_R		0.45
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-60776186;