rs371919994

Variant names:

• chr7-66629140-G-C
• rs371919994
• NM_153033.5:c.76G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-66629140-G-C
• chr7-66629140-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153033.5(KCTD7):​c.76G>C​(p.Asp26His) variant causes a missense change. The variant allele was found at a frequency of 0.000000724 in 1,381,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D26Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KCTD7 NM_153033.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P
• progressive myoclonus epilepsy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ENSG00000284461 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19646025).

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.76G>C	p.Asp26His	missense	Exon 1 of 4	NP_694578.1
	KCTD7	NM_001167961.2		c.76G>C	p.Asp26His	missense	Exon 1 of 5	NP_001161433.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD7	ENST00000639828.2	TSL:2 MANE Select	c.76G>C	p.Asp26His	missense	Exon 1 of 4	ENSP00000492240.1
	KCTD7	ENST00000443322.1	TSL:1	c.76G>C	p.Asp26His	missense	Exon 1 of 5	ENSP00000411624.1
	ENSG00000284461	ENST00000503687.2	TSL:2	n.76G>C		non_coding_transcript_exon	Exon 1 of 13	ENSP00000421074.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000593 AC: 1 AN: 168536 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381412 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 685298

African (AFR) AF: 0.00 AC: 0 AN: 28638

American (AMR) AF: 0.00 AC: 0 AN: 34706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23680

East Asian (EAS) AF: 0.00 AC: 0 AN: 31566

South Asian (SAS) AF: 0.00 AC: 0 AN: 77132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5508

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074086

Other (OTH) AF: 0.00 AC: 0 AN: 56572

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000840 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		5.2
PrimateAI	Pathogenic	0.96	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.089
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0030	B
Vest4		0.27
MutPred		0.24		Gain of catalytic residue at L28 (P = 0.0862)
MVP		0.69
ClinPred		0.46	T
GERP RS		4.0
PromoterAI		-0.054	Neutral
Varity_R		0.23
gMVP		0.33
Mutation Taster		=84/16	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: rs371919994; hg19: chr7-66094127;