11-78174139-G-A

Position:

• chr11-78174139-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001029859.3(KCTD21):​c.416C>T​(p.Ser139Phe) 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: 31)
• Consequence: KCTD21 NM_001029859.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

Genes affected

KCTD21 (HGNC:27452): (potassium channel tetramerization domain containing 21) Enables cullin family protein binding activity; histone deacetylase binding activity; and identical protein binding activity. Involved in negative regulation of smoothened signaling pathway and ubiquitin-dependent protein catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

KCTD21-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39070335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCTD21	NM_001029859.3	c.416C>T	p.Ser139Phe	missense_variant	2/2	ENST00000340067.4	NP_001025030.1
KCTD21	XM_047426803.1	c.524C>T	p.Ser175Phe	missense_variant	3/3		XP_047282759.1
KCTD21	XM_006718517.3	c.416C>T	p.Ser139Phe	missense_variant	3/3		XP_006718580.1
KCTD21	XM_006718518.4	c.416C>T	p.Ser139Phe	missense_variant	2/2		XP_006718581.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCTD21	ENST00000340067.4	c.416C>T	p.Ser139Phe	missense_variant	2/2	1	NM_001029859.3	ENSP00000339340.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.416C>T (p.S139F) alteration is located in exon 2 (coding exon 1) of the KCTD21 gene. This alteration results from a C to T substitution at nucleotide position 416, causing the serine (S) at amino acid position 139 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.065	T;T;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.79	N;N;N
REVEL	Benign	0.26
Sift	Benign	0.034	D;D;D
Sift4G	Uncertain	0.052	T;.;.
Polyphen		0.99	D;.;.
Vest4		0.42
MutPred		0.43		Loss of disorder (P = 0.002);Loss of disorder (P = 0.002);Loss of disorder (P = 0.002);
MVP		0.65
MPC		0.89
ClinPred		0.74	D
GERP RS		5.8
Varity_R		0.14
gMVP		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-77885185;