Variant 12-49544261-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_012284.3(KCNH3):c.1068C>T(p.Ser356Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,606,848 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 1 hom. )

Consequence

KCNH3
NM_012284.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.378

Variant links:

Genes affected

KCNH3 (HGNC:6252): (potassium voltage-gated channel subfamily H member 3) The protein encoded by this gene is a voltage-gated potassium channel alpha subunit predominantly expressed in the forebrain. Studies in mice have found that cognitive function increases when this gene is knocked out. In humans, the encoded protein has been shown to be capable of binding glycoprotein 120 of the human immunodeficiency virus type 1 (HIV-1) envelope. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

KCNH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-49544261-C-T is Benign according to our data. Variant chr12-49544261-C-T is described in ClinVar as [Benign]. Clinvar id is 747981.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.378 with no splicing effect.

BS2

High AC in GnomAd4 at 96 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNH3	NM_012284.3 link	c.1068C>T	p.Ser356Ser	synonymous_variant	7/15	ENST00000257981.7	NP_036416.1	Q9ULD8
KCNH3	NM_001314030.2 link	c.888C>T	p.Ser296Ser	synonymous_variant	7/15		NP_001300959.1	Q9ULD8
KCNH3	XM_011538085.3 link	c.1068C>T	p.Ser356Ser	synonymous_variant	7/15		XP_011536387.1
KCNH3	XM_047428613.1 link	c.1068C>T	p.Ser356Ser	synonymous_variant	7/10		XP_047284569.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNH3	ENST00000257981.7 link	c.1068C>T	p.Ser356Ser	synonymous_variant	7/15	1	NM_012284.3	ENSP00000257981.5	Q9ULD8
KCNH3	ENST00000551415.1 link	n.8C>T		non_coding_transcript_exon_variant	1/2	3
KCNH3	ENST00000649994.1 link	n.*678C>T		non_coding_transcript_exon_variant	8/16			ENSP00000497890.1	A0A3B3ITH0
KCNH3	ENST00000649994.1 link	n.*678C>T		3_prime_UTR_variant	8/16			ENSP00000497890.1	A0A3B3ITH0

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000956

GnomAD3 exomes

AF:

0.000156

AC:

AN:

237904

Hom.:

AF XY:

0.000100

AC XY:

AN XY:

129532

show subpopulations

Gnomad AFR exome

AF:

0.00200

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000563

Gnomad SAS exome

AF:

0.0000338

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000667

AC:

AN:

1454512

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

723430

show subpopulations

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.000630

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.000729

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.3

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over