rs869312866

Variant names:

• chr16-67320674-G-T
• rs869312866
• NM_001100915.3:c.215C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 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 VariationId is 224816.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100915.3. 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
	KCTD19	NM_001100915.3	MANE Select	c.215C>A	p.Thr72Asn	missense	Exon 2 of 16	NP_001094385.1	Q17RG1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD19	ENST00000304372.6	TSL:1 MANE Select	c.215C>A	p.Thr72Asn	missense	Exon 2 of 16	ENSP00000305702.5	Q17RG1
	KCTD19	ENST00000570049.5	TSL:1	n.234C>A		non_coding_transcript_exon	Exon 2 of 16
	KCTD19	ENST00000567976.1	TSL:4	c.200C>A	p.Thr67Asn	missense	Exon 2 of 3	ENSP00000458045.1	H3BVC0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Cerebral visual impairment and intellectual disability (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.0
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	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

Other links and lift over

dbSNP: rs869312866; hg19: chr16-67354577;