chr16-87755258-G-T

Variant names:

• chr16-87755258-G-T
• rs2303771
• NM_017566.4:c.305C>A

Variant summary

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

The NM_017566.4(KLHDC4):​c.305C>A​(p.Thr102Asn) 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. 13/22 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)
• Consequence: KLHDC4 NM_017566.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.37
• Publications: 46 publications found

Genes affected

KLHDC4 (HGNC:25272): (kelch domain containing 4)

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=0.28619093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLHDC4	NM_017566.4	c.305C>A	p.Thr102Asn	missense_variant	Exon 4 of 12	ENST00000270583.10	NP_060036.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLHDC4	ENST00000270583.10	c.305C>A	p.Thr102Asn	missense_variant	Exon 4 of 12	1	NM_017566.4	ENSP00000270583.4
KLHDC4	ENST00000567298.5	n.305C>A		non_coding_transcript_exon_variant	Exon 4 of 17	5		ENSP00000457570.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 30854

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.00054	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.83	T;T;T;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.90	.;L;L;.
PhyloP100		4.4
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;.
Polyphen		0.98	D;D;P;.
Vest4		0.41
MutPred		0.45		.;Loss of phosphorylation at T102 (P = 0.0222);Loss of phosphorylation at T102 (P = 0.0222);.;
MVP		0.50
MPC		0.065
ClinPred		0.61	D
GERP RS		1.5
Varity_R		0.42
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs2303771; hg19: chr16-87788864;