NM_000610.4:c.110A>C

Variant names:

• chr11-35176617-A-C
• NM_000610.4:c.110A>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000610.4(CD44):​c.110A>C​(p.Glu37Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CD44 NM_000610.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.38
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

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.110A>C	p.Glu37Ala	missense	Exon 2 of 18	NP_000601.3
	CD44	NM_001440324.1		c.110A>C	p.Glu37Ala	missense	Exon 2 of 18	NP_001427253.1
	CD44	NM_001440325.1		c.110A>C	p.Glu37Ala	missense	Exon 2 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.110A>C	p.Glu37Ala	missense	Exon 2 of 18	ENSP00000398632.2	P16070-1
	CD44	ENST00000415148.6	TSL:1	c.110A>C	p.Glu37Ala	missense	Exon 2 of 17	ENSP00000389830.2	P16070-4
	CD44	ENST00000433892.6	TSL:1	c.110A>C	p.Glu37Ala	missense	Exon 2 of 12	ENSP00000392331.2	P16070-10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.4
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.61		Loss of ubiquitination at K38 (P = 0.0504)
MVP		0.53
MPC		1.9
ClinPred		1.0	D
GERP RS		5.8
PromoterAI		-0.013	Neutral
Varity_R		0.90
gMVP		0.90
Mutation Taster		=16/84	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-35198164;