rs62639702

Variant names:

• chr16-23189488-C-T
• rs62639702
• NM_001039.4:c.435C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-23189488-C-T
• chr16-23189488-C-G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001039.4(SCNN1G):​c.435C>T​(p.Ser145Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,614,156 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (69 hom.)
• Consequence: SCNN1G NM_001039.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.799
• Publications: 10 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-23189488-C-T is Benign according to our data. Variant chr16-23189488-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 318347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.799 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 8 AD,AR gene

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.435C>T	p.Ser145Ser	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.435C>T	p.Ser145Ser	synonymous	Exon 3 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.435C>T	p.Ser145Ser	synonymous	Exon 2 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.435C>T	p.Ser145Ser	synonymous	Exon 3 of 13	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.00687 AC: 1046 AN: 152162 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00864

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00660 AC: 1660 AN: 251470 AF XY: 0.00668

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.00425

Gnomad ASJ exome AF: 0.000992

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00226

Gnomad NFE exome AF: 0.00859

Gnomad OTH exome AF: 0.00814

GnomAD4 exome AF: 0.00760 AC: 11110 AN: 1461876 Hom.: 69 Cov.: 43 AF XY: 0.00765 AC XY: 5560 AN XY: 727240

African (AFR) AF: 0.00702 AC: 235 AN: 33480

American (AMR) AF: 0.00420 AC: 188 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00103 AC: 27 AN: 26136

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39700

South Asian (SAS) AF: 0.00978 AC: 844 AN: 86256

European-Finnish (FIN) AF: 0.00258 AC: 138 AN: 53420

Middle Eastern (MID) AF: 0.0128 AC: 74 AN: 5768

European-Non Finnish (NFE) AF: 0.00814 AC: 9052 AN: 1111996

Other (OTH) AF: 0.00878 AC: 530 AN: 60396

GnomAD4 genome AF: 0.00690 AC: 1051 AN: 152280 Hom.: 8 Cov.: 32 AF XY: 0.00627 AC XY: 467 AN XY: 74454

African (AFR) AF: 0.00758 AC: 315 AN: 41564

American (AMR) AF: 0.00327 AC: 50 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00864 AC: 588 AN: 68024

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00779 Hom.: 2

Bravo AF: 0.00698

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.00916

EpiControl AF: 0.0101

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	1	Bronchiectasis with or without elevated sweat chloride 3;C4748251:Liddle syndrome 2;C5774176:Pseudohypoaldosteronism, type IB1, autosomal recessive (1)
-	-	1	Liddle syndrome 2 (1)
-	-	1	not specified (1)
-	-	1	Pseudohypoaldosteronism, type IB1, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.80
Mutation Taster		=99/1	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: rs62639702; hg19: chr16-23200809; COSMIC: COSV55599290;