16-23189602-C-T

Variant names:

• chr16-23189602-C-T
• rs5737
• NM_001039.4:c.549C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001039.4(SCNN1G):​c.549C>T​(p.Gly183Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 1,613,944 control chromosomes in the GnomAD database, including 4,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G183G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.065 (384 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3634 hom.)
• Consequence: SCNN1G NM_001039.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.04
• Publications: 17 publications found

Genes affected

SCNN1G (HGNC:10602): (sodium channel epithelial 1 subunit gamma) Nonvoltage-gated, amiloride-sensitive, sodium channels control fluid and electrolyte transport across epithelia in many organs. These channels are heteromeric complexes consisting of 3 subunits: alpha, beta, and gamma. This gene encodes the gamma subunit, and mutations in this gene have been associated with Liddle syndrome. [provided by RefSeq, Apr 2009]

SCNN1G Gene-Disease associations (from GenCC):

• Liddle syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• bronchiectasis with or without elevated sweat chloride 3

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• Liddle syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• pseudohypoaldosteronism, type IB1, autosomal recessive

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-23189602-C-T is Benign according to our data. Variant chr16-23189602-C-T is described in ClinVar as Benign. ClinVar VariationId is 165174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039.4. 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
	SCNN1G	NM_001039.4	MANE Select	c.549C>T	p.Gly183Gly	synonymous	Exon 3 of 13	NP_001030.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCNN1G	ENST00000300061.3	TSL:1 MANE Select	c.549C>T	p.Gly183Gly	synonymous	Exon 3 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.549C>T	p.Gly183Gly	synonymous	Exon 2 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.549C>T	p.Gly183Gly	synonymous	Exon 3 of 13	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9882 AN: 152130 Hom.: 380 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0185

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0739

Gnomad OTH AF: 0.0616

GnomAD2 exomes AF: 0.0612 AC: 15397 AN: 251492 AF XY: 0.0613

Gnomad AFR exome AF: 0.0512

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0638

Gnomad EAS exome AF: 0.0175

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.0732

Gnomad OTH exome AF: 0.0668

GnomAD4 exome AF: 0.0670 AC: 97911 AN: 1461696 Hom.: 3634 Cov.: 34 AF XY: 0.0662 AC XY: 48146 AN XY: 727160

African (AFR) AF: 0.0503 AC: 1684 AN: 33478

American (AMR) AF: 0.0366 AC: 1636 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 1620 AN: 26136

East Asian (EAS) AF: 0.0151 AC: 600 AN: 39700

South Asian (SAS) AF: 0.0340 AC: 2932 AN: 86256

European-Finnish (FIN) AF: 0.126 AC: 6749 AN: 53420

Middle Eastern (MID) AF: 0.0664 AC: 383 AN: 5768

European-Non Finnish (NFE) AF: 0.0704 AC: 78257 AN: 1111820

Other (OTH) AF: 0.0671 AC: 4050 AN: 60394

GnomAD4 genome AF: 0.0651 AC: 9906 AN: 152248 Hom.: 384 Cov.: 32 AF XY: 0.0663 AC XY: 4938 AN XY: 74428

African (AFR) AF: 0.0523 AC: 2174 AN: 41560

American (AMR) AF: 0.0506 AC: 774 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.0188 AC: 97 AN: 5170

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4830

European-Finnish (FIN) AF: 0.123 AC: 1305 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0739 AC: 5029 AN: 68012

Other (OTH) AF: 0.0614 AC: 130 AN: 2116

Alfa AF: 0.0686 Hom.: 280

Bravo AF: 0.0591

Asia WGS AF: 0.0620 AC: 214 AN: 3478

EpiCase AF: 0.0641

EpiControl AF: 0.0715

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	not specified (2)
-	-	1	Liddle syndrome 2 (1)
-	-	1	Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.082
DANN	Benign	0.50
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs5737; hg19: chr16-23200923; COSMIC: COSV55602542;