NM_015198.5:c.3320C>A

Variant names:

• chr7-51027776-G-T
• rs758641946
• NM_015198.5:c.3320C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015198.5(COBL):​c.3320C>A​(p.Thr1107Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. T1107R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COBL NM_015198.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74
• Publications: 0 publications found

Genes affected

COBL (HGNC:22199): (cordon-bleu WH2 repeat protein) This gene encodes a protein that contains WH2 domains (WASP, Wiskott-Aldrich syndrome protein, homology domain-2) that interact with actin. The encoded actin regulator protein is required for growth and assembly of brush border microvilli that play a role in maintaining intestinal homeostasis. A similar protein in mouse functions in midbrain neural tube closure. A pseudogene of this gene is located on chromosome X. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2865289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015198.5. 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
	COBL	NM_015198.5	MANE Select	c.3320C>A	p.Thr1107Lys	missense	Exon 10 of 13	NP_056013.2
	COBL	NM_001410881.1		c.3566C>A	p.Thr1189Lys	missense	Exon 12 of 15	NP_001397810.1	O75128-2
	COBL	NM_001287436.3		c.3491C>A	p.Thr1164Lys	missense	Exon 11 of 14	NP_001274365.1	O75128-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COBL	ENST00000265136.12	TSL:1 MANE Select	c.3320C>A	p.Thr1107Lys	missense	Exon 10 of 13	ENSP00000265136.7	O75128-1
	COBL	ENST00000431948.6	TSL:1	c.3566C>A	p.Thr1189Lys	missense	Exon 12 of 15	ENSP00000413498.2	O75128-2
	COBL	ENST00000395542.6	TSL:1	c.3491C>A	p.Thr1164Lys	missense	Exon 11 of 14	ENSP00000378912.3	O75128-7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.7
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.30		Loss of loop (P = 9e-04)
MVP		0.39
MPC		0.38
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.35
gMVP		0.57
Mutation Taster		=84/16	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: rs758641946; hg19: chr7-51095473;