chr7-66628895-G-A

Variant names:

• chr7-66628895-G-A
• rs191169882
• NM_153033.5:c.-170G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_153033.5(KCTD7):​c.-170G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 530,832 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.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: KCTD7 NM_153033.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490
• 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: 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00156 (237/152152) while in subpopulation AFR AF = 0.00549 (228/41520). AF 95% confidence interval is 0.00491. There are 0 homozygotes in GnomAd4. There are 112 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCTD7	NM_153033.5	c.-170G>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000639828.2	NP_694578.1
KCTD7	NM_001167961.2	c.-170G>A		5_prime_UTR_variant	Exon 1 of 5		NP_001161433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCTD7	ENST00000639828.2	c.-170G>A		5_prime_UTR_variant	Exon 1 of 4	2	NM_153033.5	ENSP00000492240.1
ENSG00000284461	ENST00000503687.2	n.-170G>A		upstream_gene_variant		2		ENSP00000421074.1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 237 AN: 152046 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00551

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome AF: 0.000129 AC: 49 AN: 378680 Hom.: 0 Cov.: 5 AF XY: 0.000108 AC XY: 21 AN XY: 194540

African (AFR) AF: 0.00469 AC: 38 AN: 8106

American (AMR) AF: 0.000306 AC: 2 AN: 6542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9094

East Asian (EAS) AF: 0.00 AC: 0 AN: 20028

South Asian (SAS) AF: 0.00 AC: 0 AN: 18074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1478

European-Non Finnish (NFE) AF: 0.00000736 AC: 2 AN: 271856

Other (OTH) AF: 0.000348 AC: 7 AN: 20112

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152152 Hom.: 0 Cov.: 30 AF XY: 0.00151 AC XY: 112 AN XY: 74376

African (AFR) AF: 0.00549 AC: 228 AN: 41520

American (AMR) AF: 0.000523 AC: 8 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.5
DANN	Benign	0.84
PhyloP100		-0.49
PromoterAI		-0.058	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs191169882; hg19: chr7-66093882;