chr11-35189886-C-A

Variant names:

• chr11-35189886-C-A
• rs61752930
• NM_000610.4:c.488C>A

Variant summary

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

The NM_000610.4(CD44):​c.488C>A​(p.Thr163Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T163M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CD44 NM_000610.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 2 publications found

Genes affected

CD44 (HGNC:1681): (CD44 molecule (IN blood group)) The protein encoded by this gene is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000610.4. 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
	CD44	NM_000610.4	MANE Select	c.488C>A	p.Thr163Lys	missense	Exon 5 of 18	NP_000601.3
	CD44	NM_001440324.1		c.488C>A	p.Thr163Lys	missense	Exon 5 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.488C>A	p.Thr163Lys	missense	Exon 5 of 18	NP_001427254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD44	ENST00000428726.8	TSL:1 MANE Select	c.488C>A	p.Thr163Lys	missense	Exon 5 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.488C>A	p.Thr163Lys	missense	Exon 5 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.488C>A	p.Thr163Lys	missense	Exon 5 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 251168 AF XY: 0.0000442

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111970

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.013	D
Polyphen		0.99	D
Vest4		0.68
MutPred		0.41		Gain of ubiquitination at T163 (P = 0.0029)
MVP		0.38
MPC		0.31
ClinPred		0.86	D
GERP RS		4.9
PromoterAI		-0.027	Neutral
Varity_R		0.93
gMVP		0.81
Mutation Taster		=81/19	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

dbSNP: rs61752930; hg19: chr11-35211433;