rs5729

Variant names:

• chr16-23216075-T-A
• rs5729
• NM_001039.4:c.*606T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039.4(SCNN1G):​c.*606T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 161,576 control chromosomes in the GnomAD database, including 3,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3528 hom., cov: 33)
  • Exomes 𝑓: 0.12 (82 hom.)
• Consequence: SCNN1G NM_001039.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.388
• 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
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-23216075-T-A is Benign according to our data. Variant chr16-23216075-T-A is described in ClinVar as Benign. ClinVar VariationId is 318370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 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.*606T>A		3_prime_UTR	Exon 13 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.*606T>A		3_prime_UTR	Exon 13 of 13	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876142.1		c.*606T>A		3_prime_UTR	Exon 12 of 12	ENSP00000546201.1
	SCNN1G	ENST00000876141.1		c.*606T>A		3_prime_UTR	Exon 13 of 13	ENSP00000546200.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32186 AN: 152046 Hom.: 3519 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.117 AC: 1102 AN: 9412 Hom.: 82 Cov.: 0 AF XY: 0.112 AC XY: 531 AN XY: 4744

African (AFR) AF: 0.188 AC: 15 AN: 80

American (AMR) AF: 0.0864 AC: 159 AN: 1840

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 8 AN: 68

East Asian (EAS) AF: 0.0128 AC: 5 AN: 390

South Asian (SAS) AF: 0.0336 AC: 27 AN: 804

European-Finnish (FIN) AF: 0.100 AC: 20 AN: 200

Middle Eastern (MID) AF: 0.100 AC: 2 AN: 20

European-Non Finnish (NFE) AF: 0.146 AC: 818 AN: 5602

Other (OTH) AF: 0.118 AC: 48 AN: 408

GnomAD4 genome AF: 0.212 AC: 32224 AN: 152164 Hom.: 3528 Cov.: 33 AF XY: 0.208 AC XY: 15504 AN XY: 74400

African (AFR) AF: 0.246 AC: 10210 AN: 41496

American (AMR) AF: 0.162 AC: 2485 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.0611 AC: 317 AN: 5188

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4828

European-Finnish (FIN) AF: 0.232 AC: 2451 AN: 10582

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14930 AN: 67990

Other (OTH) AF: 0.216 AC: 454 AN: 2106

Alfa AF: 0.226 Hom.: 511

Bravo AF: 0.207

Asia WGS AF: 0.110 AC: 381 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (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	1.1
DANN	Benign	0.60
PhyloP100		-0.39
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: rs5729; hg19: chr16-23227396;