13-45194300-G-C

Variant names:

• chr13-45194300-G-C
• rs1872777609
• NM_198404.3:c.268C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198404.3(KCTD4):​c.268C>G​(p.Leu90Val) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCTD4 NM_198404.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.82
• Publications: 0 publications found

Genes affected

KCTD4 (HGNC:23227): (potassium channel tetramerization domain containing 4) Predicted to be involved in protein homooligomerization. [provided by Alliance of Genome Resources, Apr 2022]

GTF2F2 (HGNC:4653): (general transcription factor IIF subunit 2) Predicted to enable RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in microtubule cytoskeleton and nucleoplasm. Part of transcription preinitiation complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198404.3. 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
	KCTD4	NM_198404.3	MANE Select	c.268C>G	p.Leu90Val	missense	Exon 2 of 2	NP_940686.2	Q8WVF5
	GTF2F2	NM_004128.3	MANE Select	c.305-13124G>C		intron	N/A	NP_004119.1	P13984

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCTD4	ENST00000379108.2	TSL:6 MANE Select	c.268C>G	p.Leu90Val	missense	Exon 2 of 2	ENSP00000368402.1	Q8WVF5
	GTF2F2	ENST00000340473.8	TSL:1 MANE Select	c.305-13124G>C		intron	N/A	ENSP00000340823.6	P13984
	GTF2F2	ENST00000883031.1		c.382+10822G>C		intron	N/A	ENSP00000553090.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	D
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		6.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.0	D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.85
MutPred		0.82		Gain of catalytic residue at R87 (P = 0.1354)
MVP		0.90
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.76
gMVP		0.79
Mutation Taster		=44/56	disease causing

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: rs1872777609; hg19: chr13-45768435;