KLHDC4 p.Thr102Ser

Variant names:

• chr16-87755259-T-A
• NM_017566.4:c.304A>T
• KLHDC4 p.Thr102Ser

Your query was ambiguous. Multiple possible variants found:

• chr16-87755259-T-A
• chr16-87755258-G-C
• chr16-87755257-GGT-AGA
• chr16-87755257-GGT-TGA
• chr16-87755257-GGT-CGA
• chr16-87755257-GG-AC

Variant summary

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

The NM_017566.4(KLHDC4):​c.304A>T​(p.Thr102Ser) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHDC4 NM_017566.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.30
• Publications: 0 publications found

Genes affected

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

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_017566.4. 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
	KLHDC4	NM_017566.4	MANE Select	c.304A>T	p.Thr102Ser	missense	Exon 4 of 12	NP_060036.2
	KLHDC4	NM_001184856.2		c.304A>T	p.Thr102Ser	missense	Exon 4 of 11	NP_001171785.1	Q8TBB5-3
	KLHDC4	NM_001184854.2		c.133A>T	p.Thr45Ser	missense	Exon 2 of 10	NP_001171783.1	Q8TBB5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHDC4	ENST00000270583.10	TSL:1 MANE Select	c.304A>T	p.Thr102Ser	missense	Exon 4 of 12	ENSP00000270583.4	Q8TBB5-1
	KLHDC4	ENST00000347925.9	TSL:1	c.304A>T	p.Thr102Ser	missense	Exon 4 of 11	ENSP00000325717.5	Q8TBB5-3
	KLHDC4	ENST00000353170.9	TSL:1	c.133A>T	p.Thr45Ser	missense	Exon 2 of 10	ENSP00000262530.5	Q8TBB5-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0057	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.32
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.49		Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-87788865;