chr16-23189440-T-C

Variant names:

• chr16-23189440-T-C
• rs5734
• NM_001039.4:c.387T>C

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.387T>C​(p.Tyr129Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,870 control chromosomes in the GnomAD database, including 76,394 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6188 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70206 hom.)
• Consequence: SCNN1G NM_001039.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.39
• Publications: 22 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
• Liddle syndrome 2

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

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, 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=-0.89).
• BP6: Variant 16-23189440-T-C is Benign according to our data. Variant chr16-23189440-T-C is described in ClinVar as Benign. ClinVar VariationId is 165172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 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.387T>C	p.Tyr129Tyr	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.387T>C	p.Tyr129Tyr	synonymous	Exon 3 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.387T>C	p.Tyr129Tyr	synonymous	Exon 2 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.387T>C	p.Tyr129Tyr	synonymous	Exon 3 of 13	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41404 AN: 152000 Hom.: 6165 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.276

GnomAD2 exomes AF: 0.309 AC: 77645 AN: 251300 AF XY: 0.305

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.314

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.306 AC: 447170 AN: 1461752 Hom.: 70206 Cov.: 42 AF XY: 0.305 AC XY: 221919 AN XY: 727182

African (AFR) AF: 0.148 AC: 4948 AN: 33478

American (AMR) AF: 0.431 AC: 19282 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8016 AN: 26136

East Asian (EAS) AF: 0.162 AC: 6422 AN: 39700

South Asian (SAS) AF: 0.271 AC: 23379 AN: 86256

European-Finnish (FIN) AF: 0.369 AC: 19678 AN: 53392

Middle Eastern (MID) AF: 0.273 AC: 1567 AN: 5744

European-Non Finnish (NFE) AF: 0.311 AC: 345510 AN: 1111932

Other (OTH) AF: 0.304 AC: 18368 AN: 60390

GnomAD4 genome AF: 0.273 AC: 41478 AN: 152118 Hom.: 6188 Cov.: 32 AF XY: 0.274 AC XY: 20398 AN XY: 74346

African (AFR) AF: 0.158 AC: 6551 AN: 41530

American (AMR) AF: 0.356 AC: 5446 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3468

East Asian (EAS) AF: 0.180 AC: 927 AN: 5156

South Asian (SAS) AF: 0.268 AC: 1290 AN: 4808

European-Finnish (FIN) AF: 0.362 AC: 3824 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21462 AN: 67980

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.309 Hom.: 4919

Bravo AF: 0.269

Asia WGS AF: 0.274 AC: 950 AN: 3478

EpiCase AF: 0.306

EpiControl AF: 0.307

ClinVar

ClinVar submissions

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	-0.89
CADD	Benign	0.036
DANN	Benign	0.26
PhyloP100		-1.4
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: rs5734; hg19: chr16-23200761; COSMIC: COSV55597758;