chr6-39316274-G-C

Variant names:

• chr6-39316274-G-C
• rs1535500
• NM_001135106.2:c.830C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001135106.2(KCNK16):​c.830C>G​(p.Ala277Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNK16 NM_001135106.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 107 publications found

Genes affected

KCNK16 (HGNC:14464): (potassium two pore domain channel subfamily K member 16) The protein encoded by this gene belongs to the family of potassium channel proteins containing two pore-forming P domains. This channel is an open rectifier which primarily passes outward current under physiological K+ concentrations. This gene is expressed predominantly in the pancreas and is activated at alkaline pH. Several alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Sep 2008]

LOC105375047 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070254564).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135106.2. 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
	KCNK16	NM_001135106.2	MANE Select	c.830C>G	p.Ala277Gly	missense	Exon 5 of 5	NP_001128578.1	Q96T55-3
	KCNK16	NM_001135105.2		c.661+508C>G		intron	N/A	NP_001128577.1	Q96T55-4
	KCNK16	NM_032115.4		c.802+28C>G		intron	N/A	NP_115491.1	Q96T55-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNK16	ENST00000437525.3	TSL:1 MANE Select	c.830C>G	p.Ala277Gly	missense	Exon 5 of 5	ENSP00000415375.2	Q96T55-3
	KCNK16	ENST00000425054.6	TSL:1	c.661+508C>G		intron	N/A	ENSP00000391498.2	Q96T55-4
	KCNK16	ENST00000373229.9	TSL:1	c.802+28C>G		intron	N/A	ENSP00000362326.5	Q96T55-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.52
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.23
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.036
Sift	Benign	0.33	T
Sift4G	Benign	0.33	T
Vest4		0.082
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.15
ClinPred		0.047	T
GERP RS		1.9
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1535500; hg19: chr6-39284050;