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. Variant got 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.

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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COBL	NM_015198.5	c.3320C>A	p.Thr1107Lys	missense_variant	Exon 10 of 13	ENST00000265136.12	NP_056013.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COBL	ENST00000265136.12	c.3320C>A	p.Thr1107Lys	missense_variant	Exon 10 of 13	1	NM_015198.5	ENSP00000265136.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;D;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	.;.;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.7	D;D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		1.0, 1.0	.;.;D;D
Vest4		0.41, 0.59
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs758641946; hg19: chr7-51095473;