14-44945261-C-G

Variant names:

• chr14-44945261-C-G
• NM_017658.5:c.668G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017658.5(KLHL28):​c.668G>C​(p.Ser223Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLHL28 NM_017658.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24733037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL28	NM_017658.5	c.668G>C	p.Ser223Thr	missense_variant	Exon 2 of 5	ENST00000396128.9	NP_060128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL28	ENST00000396128.9	c.668G>C	p.Ser223Thr	missense_variant	Exon 2 of 5	1	NM_017658.5	ENSP00000379434.4
KLHL28	ENST00000355081.3	c.710G>C	p.Ser237Thr	missense_variant	Exon 2 of 5	1		ENSP00000347193.2
KLHL28	ENST00000579157.1	c.668G>C	p.Ser223Thr	missense_variant	Exon 3 of 3	2		ENSP00000462025.1
KLHL28	ENST00000556500.1	c.*180G>C		downstream_gene_variant		4		ENSP00000452061.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461752 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.054	T;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.0053
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.74	N;N;.
REVEL	Benign	0.065
Sift	Benign	0.34	T;T;.
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0050	B;.;.
Vest4		0.34
MutPred		0.58		Gain of catalytic residue at L226 (P = 9e-04);.;Gain of catalytic residue at L226 (P = 9e-04);
MVP		0.68
MPC		0.57
ClinPred		0.49	T
GERP RS		4.8
Varity_R		0.20
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-45414464;