chr16-23182544-A-C

Variant names:

• chr16-23182544-A-C
• rs5718
• ENST00000648673.1:n.194-973T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000648673.1(ENSG00000285613):​n.194-973T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 35)
• Consequence: ENSG00000285613 ENST00000648673.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 14 publications found

Genes affected

ENSG00000285613 (HGNC:):

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648673.1. 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.-314A>C		upstream_gene	N/A	NP_001030.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285613	ENST00000648673.1		n.194-973T>G		intron	N/A
	SCNN1G	ENST00000300061.3	TSL:1 MANE Select	c.-314A>C		upstream_gene	N/A	ENSP00000300061.2	P51170
	SCNN1G	ENST00000876141.1		c.-314A>C		upstream_gene	N/A	ENSP00000546200.1

Frequencies

GnomAD3 genomes Cov.: 35

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

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.8
DANN	Benign	0.33
PhyloP100		0.42
PromoterAI		0.039	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5718; hg19: chr16-23193865;