rs1179943912

Variant names:

• chr14-44934503-T-C
• rs1179943912
• NM_017658.5:c.955A>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.955A>G​(p.Ile319Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: KLHL28 NM_017658.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.56
• Publications: 1 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=0.10381469).

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.955A>G	p.Ile319Val	missense	Exon 3 of 5	NP_060128.2
	KLHL28	NM_001308112.2		c.997A>G	p.Ile333Val	missense	Exon 3 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.955A>G	p.Ile319Val	missense	Exon 3 of 5	ENSP00000379434.4	Q9NXS3-1
	KLHL28	ENST00000355081.3	TSL:1	c.997A>G	p.Ile333Val	missense	Exon 3 of 5	ENSP00000347193.2	J3KNY7
	KLHL28	ENST00000945248.1		c.955A>G	p.Ile319Val	missense	Exon 3 of 6	ENSP00000615307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249842 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460562 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726514

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111356

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	0.076
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.36	N
PhyloP100		3.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.15
Sift	Benign	0.54	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.45		Gain of catalytic residue at L317 (P = 0)
MVP		0.52
MPC		0.48
ClinPred		0.21	T
GERP RS		5.4
Varity_R		0.057
gMVP		0.31
Mutation Taster		=95/4	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: rs1179943912; hg19: chr14-45403706;