chr14-44945054-G-C

Variant names:

• chr14-44945054-G-C
• NM_017658.5:c.875C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017658.5(KLHL28):​c.875C>G​(p.Ser292Cys) 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 benign 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: 9.51
• Publications: 0 publications found

Genes affected

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

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26155385).

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.875C>G	p.Ser292Cys	missense	Exon 2 of 5	NP_060128.2
	KLHL28	NM_001308112.2		c.917C>G	p.Ser306Cys	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.875C>G	p.Ser292Cys	missense	Exon 2 of 5	ENSP00000379434.4	Q9NXS3-1
	KLHL28	ENST00000355081.3	TSL:1	c.917C>G	p.Ser306Cys	missense	Exon 2 of 5	ENSP00000347193.2	J3KNY7
	KLHL28	ENST00000945248.1		c.875C>G	p.Ser292Cys	missense	Exon 2 of 6	ENSP00000615307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.20
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.68	N
PhyloP100		9.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.21
Sift	Benign	0.17	T
Sift4G	Benign	0.063	T
Polyphen		0.015	B
Vest4		0.31
MutPred		0.46		Gain of catalytic residue at K291 (P = 0)
MVP		0.77
MPC		0.81
ClinPred		0.60	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.59
Mutation Taster		=48/52	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr14-45414257;