NM_153033.5:c.594C>G

Variant names:

• chr7-66638956-C-G
• rs749192199
• NM_153033.5:c.594C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_153033.5(KCTD7):​c.594C>G​(p.Pro198Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P198P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD7 NM_153033.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.86
• 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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000284461 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1186184).
• BP6: Variant 7-66638956-C-G is Benign according to our data. Variant chr7-66638956-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 536953.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.86 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.594C>G	p.Pro198Pro	synonymous_variant	Exon 4 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.594C>G	p.Pro198Pro	synonymous_variant	Exon 4 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.594C>G	p.Pro198Pro	synonymous_variant	Exon 4 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.397+27C>G		intron_variant	Intron 3 of 12	2		ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Progressive myoclonic epilepsy type 3 Benign:1

Apr 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.8
DANN	Benign	0.71
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.12	T
PhyloP100		2.9
GERP RS		3.4
PromoterAI		-0.0011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs749192199; hg19: chr7-66103943;