KCTD7 p.Gly135Arg

Variant names:

• chr7-66638341-G-C
• NM_153033.5:c.403G>C
• KCTD7 p.Gly135Arg

Your query was ambiguous. Multiple possible variants found:

• chr7-66638341-G-C
• chr7-66638341-G-A
• chr7-66638341-GGG-CGT
• chr7-66638341-GGG-CGC
• chr7-66638341-GGG-CGA
• chr7-66638341-GGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153033.5(KCTD7):​c.403G>C​(p.Gly135Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G135G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27
• Publications: 0 publications found

Genes affected

KCTD7 (HGNC:21957): (potassium channel tetramerization domain containing 7) This gene encodes a member of the potassium channel tetramerization domain-containing protein family. Family members are identified on a structural basis and contain an amino-terminal domain similar to the T1 domain present in the voltage-gated potassium channel. Mutations in this gene have been associated with progressive myoclonic epilepsy-3. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

KCTD7 Gene-Disease associations (from GenCC):

• progressive myoclonic epilepsy type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000284461 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153033.5. 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
	KCTD7	NM_153033.5	MANE Select	c.403G>C	p.Gly135Arg	missense	Exon 3 of 4	NP_694578.1	Q96MP8-1
	KCTD7	NM_001167961.2		c.403G>C	p.Gly135Arg	missense	Exon 3 of 5	NP_001161433.1	Q96MP8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.403G>C	p.Gly135Arg	missense	Exon 3 of 4	ENSP00000492240.1	Q96MP8-1
	KCTD7	ENST00000443322.1	TSL:1	c.403G>C	p.Gly135Arg	missense	Exon 3 of 5	ENSP00000411624.1	Q96MP8-2
	ENSG00000284461	ENST00000503687.2	TSL:2	n.233G>C		non_coding_transcript_exon	Exon 2 of 13	ENSP00000421074.1	E9PHB8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0093	T
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.95	L
PhyloP100		7.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	1.2	N
REVEL	Uncertain	0.49
Sift	Benign	0.20	T
Sift4G	Benign	0.51	T
Varity_R		0.15
gMVP		0.80
Mutation Taster		=36/64	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

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

Other links and lift over

hg19: chr7-66103328;