NM_017658.5:c.1531C>G

Variant names:

• chr14-44931354-G-C
• rs985456794
• NM_017658.5:c.1531C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017658.5(KLHL28):​c.1531C>G​(p.Pro511Ala) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P511S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: KLHL28 NM_017658.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.31
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3575281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHL28	NM_017658.5	c.1531C>G	p.Pro511Ala	missense_variant	Exon 4 of 5	ENST00000396128.9	NP_060128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHL28	ENST00000396128.9	c.1531C>G	p.Pro511Ala	missense_variant	Exon 4 of 5	1	NM_017658.5	ENSP00000379434.4
KLHL28	ENST00000355081.3	c.1573C>G	p.Pro525Ala	missense_variant	Exon 4 of 5	1		ENSP00000347193.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.8	L;.
PhyloP100		6.3
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.48
Sift	Benign	0.79	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.98	D;.
Vest4		0.41
MutPred		0.49		Gain of catalytic residue at V508 (P = 0.0014);.;
MVP		0.82
MPC		0.77
ClinPred		0.56	D
GERP RS		3.9
Varity_R		0.16
gMVP		0.30
Mutation Taster		=59/41	polymorphism

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

dbSNP: rs985456794; hg19: chr14-45400557;