rs377423129

Variant names:

• chr14-44929063-A-C
• rs377423129
• NM_017658.5:c.1681T>G

Your query was ambiguous. Multiple possible variants found:

• chr14-44929063-A-C
• chr14-44929063-A-G

Variant summary

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

The NM_017658.5(KLHL28):​c.1681T>G​(p.Tyr561Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,782 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Y561H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KLHL28 NM_017658.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.82
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1681T>G	p.Tyr561Asp	missense	Exon 5 of 5	NP_060128.2
	KLHL28	NM_001308112.2		c.1723T>G	p.Tyr575Asp	missense	Exon 5 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.1681T>G	p.Tyr561Asp	missense	Exon 5 of 5	ENSP00000379434.4	Q9NXS3-1
	KLHL28	ENST00000355081.3	TSL:1	c.1723T>G	p.Tyr575Asp	missense	Exon 5 of 5	ENSP00000347193.2	J3KNY7
	KLHL28	ENST00000945248.1		c.1756T>G	p.Tyr586Asp	missense	Exon 6 of 6	ENSP00000615307.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461782 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111946

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Benign	0.33	N
PhyloP100		6.8
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.47
Sift	Benign	0.093	T
Sift4G	Benign	0.29	T
Polyphen		0.99	D
Vest4		0.50
MutPred		0.53		Gain of catalytic residue at A557 (P = 0)
MVP		0.84
MPC		1.1
ClinPred		0.92	D
GERP RS		4.6
Varity_R		0.22
gMVP		0.78
Mutation Taster		=49/51	disease causing

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: rs377423129; hg19: chr14-45398266;