rs869312866

chr16-67320674-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The NM_001100915.3(KCTD19):c.215C>A(p.Thr72Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD19 NM_001100915.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.95

Genes affected

KCTD19 (HGNC:24753): (potassium channel tetramerization domain containing 19) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807
• PP5: Variant 16-67320674-G-T is Pathogenic according to our data. Variant chr16-67320674-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 224816.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-67320674-G-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCTD19	NM_001100915.3	c.215C>A	p.Thr72Asn	missense_variant	2/16	ENST00000304372.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCTD19	ENST00000304372.6	c.215C>A	p.Thr72Asn	missense_variant	2/16	1	NM_001100915.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebral visual impairment and intellectual disability Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Sep 09, 2015

This study shows that diverse genetic causes underlie CVI. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	27
Dann	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.4	N;D;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.010	D;T;.
Sift4G	Pathogenic	0.0	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.67
MutPred		0.74		Gain of catalytic residue at T72 (P = 0.0478);.;.;
MVP		0.91
MPC		1.0
ClinPred		0.95	D
GERP RS		6.1
Varity_R		0.31
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs869312866; hg19: chr16-67354577;