14-44945147-T-C

Variant names:

• chr14-44945147-T-C
• NM_017658.5:c.782A>G

Variant summary

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

The NM_017658.5(KLHL28):​c.782A>G​(p.His261Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: KLHL28 NM_017658.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.62
• Publications: 0 publications found

Genes affected

KLHL28 (HGNC:19741): (kelch like family member 28)

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, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017658.5. 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
	KLHL28	NM_017658.5	MANE Select	c.782A>G	p.His261Arg	missense	Exon 2 of 5	NP_060128.2
	KLHL28	NM_001308112.2		c.824A>G	p.His275Arg	missense	Exon 2 of 5	NP_001295041.1	J3KNY7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL28	ENST00000396128.9	TSL:1 MANE Select	c.782A>G	p.His261Arg	missense	Exon 2 of 5	ENSP00000379434.4	Q9NXS3-1
	KLHL28	ENST00000355081.3	TSL:1	c.824A>G	p.His275Arg	missense	Exon 2 of 5	ENSP00000347193.2	J3KNY7
	KLHL28	ENST00000945248.1		c.782A>G	p.His261Arg	missense	Exon 2 of 6	ENSP00000615307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.79
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Pathogenic	0.67
Sift	Benign	0.089	T
Sift4G	Benign	0.38	T
Polyphen		0.053	B
Vest4		0.86
MutPred		0.49		Gain of catalytic residue at P264 (P = 0.0135)
MVP		0.83
MPC		1.0
ClinPred		0.91	D
GERP RS		5.6
Varity_R		0.59
gMVP		0.86
Mutation Taster		=38/62	disease causing

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

hg19: chr14-45414350;