chr14-44934476-C-A

Variant names:

• chr14-44934476-C-A
• NM_017658.5:c.982G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017658.5(KLHL28):​c.982G>T​(p.Val328Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 4.57

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL28	NM_017658.5	c.982G>T	p.Val328Phe	missense_variant	Exon 3 of 5	ENST00000396128.9	NP_060128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL28	ENST00000396128.9	c.982G>T	p.Val328Phe	missense_variant	Exon 3 of 5	1	NM_017658.5	ENSP00000379434.4
KLHL28	ENST00000355081.3	c.1024G>T	p.Val342Phe	missense_variant	Exon 3 of 5	1		ENSP00000347193.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461638 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

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	0.29
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.83	D;D
MetaSVM	Uncertain	-0.00050	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Pathogenic	0.67
Sift	Benign	0.048	D;D
Sift4G	Benign	0.71	T;T
Polyphen		0.17	B;.
Vest4		0.91
MutPred		0.60		Gain of catalytic residue at L329 (P = 0.0048);.;
MVP		0.86
MPC		0.84
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.70
gMVP		0.89

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: chr14-45403679;