11-61008631-T-A

Variant names:

• chr11-61008631-T-A
• rs61899223
• NM_006725.5:c.567T>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006725.5(CD6):​c.567T>A​(p.Thr189Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T189T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CD6 NM_006725.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.178).
• BP7: Synonymous conserved (PhyloP=-0.593 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006725.5. 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
	CD6	NM_006725.5	MANE Select	c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 13	NP_006716.3	P30203-1
	CD6	NM_001254750.2		c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 11	NP_001241679.1	P30203-4
	CD6	NM_001254751.2		c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 11	NP_001241680.1	P30203-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD6	ENST00000313421.11	TSL:1 MANE Select	c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 13	ENSP00000323280.7	P30203-1
	CD6	ENST00000352009.9	TSL:1	c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 11	ENSP00000340628.5	P30203-4
	CD6	ENST00000452451.6	TSL:1	c.567T>A	p.Thr189Thr	synonymous	Exon 4 of 11	ENSP00000390676.2	P30203-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455500 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723496

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 85252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109530

Other (OTH) AF: 0.0000166 AC: 1 AN: 60150

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.58
PhyloP100		-0.59
PromoterAI		0.091	Neutral

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

dbSNP: rs61899223; hg19: chr11-60776103;