NM_170741.4:c.-94+219C>A

Variant names:

• chr17-70131194-C-A
• rs1251037571
• NM_170741.4:c.-94+219C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BP6_Very_Strong

The NM_170741.4(KCNJ16):​c.-94+219C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (0 hom., cov: 15)
  • Failed GnomAD Quality Control
• Consequence: KCNJ16 NM_170741.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.14
• Publications: 0 publications found

Genes affected

KCNJ16 (HGNC:6262): (potassium inwardly rectifying channel subfamily J member 16) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which tends to allow potassium to flow into rather than out of a cell, can form heterodimers with two other inward-rectifier type potassium channels. It may function in fluid and pH balance regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

KCNJ16 Gene-Disease associations (from GenCC):

• hypokalemic alkalosis, familial, with specific renal tubulopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hypokalemic tubulopathy and deafness

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 17-70131194-C-A is Benign according to our data. Variant chr17-70131194-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1317397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170741.4. 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
	KCNJ16	NM_170741.4	MANE Select	c.-94+219C>A		intron	N/A	NP_733937.3	Q9NPI9
	KCNJ16	NM_001270422.2		c.-221-159C>A		intron	N/A	NP_001257351.1	Q9NPI9
	KCNJ16	NM_001291622.3		c.-94+219C>A		intron	N/A	NP_001278551.2	Q9NPI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ16	ENST00000392671.6	TSL:2 MANE Select	c.-94+219C>A		intron	N/A	ENSP00000376439.1	Q9NPI9
	KCNJ16	ENST00000283936.5	TSL:1	c.-94+219C>A		intron	N/A	ENSP00000283936.1	Q9NPI9
	KCNJ16	ENST00000392670.5	TSL:1	c.-94+219C>A		intron	N/A	ENSP00000376438.1	Q9NPI9

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 1487 AN: 83864 Hom.: 0 Cov.: 15

Gnomad AFR AF: 0.00792

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00933

Gnomad SAS AF: 0.0167

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0217

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0124

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0178 AC: 1489 AN: 83862 Hom.: 0 Cov.: 15 AF XY: 0.0173 AC XY: 695 AN XY: 40122

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00794 AC: 231 AN: 29094

American (AMR) AF: 0.0184 AC: 142 AN: 7738

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 37 AN: 1758

East Asian (EAS) AF: 0.00938 AC: 33 AN: 3518

South Asian (SAS) AF: 0.0168 AC: 43 AN: 2560

European-Finnish (FIN) AF: 0.0215 AC: 72 AN: 3348

Middle Eastern (MID) AF: 0.0234 AC: 3 AN: 128

European-Non Finnish (NFE) AF: 0.0263 AC: 897 AN: 34124

Other (OTH) AF: 0.0123 AC: 14 AN: 1138

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.70
PhyloP100		2.1
Mutation Taster		=100/0	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: rs1251037571; hg19: chr17-68127335;