16-23186359-C-G

Variant names:

• chr16-23186359-C-G
• rs373976756
• NM_001039.4:c.88C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039.4(SCNN1G):​c.88C>G​(p.Arg30Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SCNN1G NM_001039.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

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]

ENSG00000285613 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23836178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1G	NM_001039.4	c.88C>G	p.Arg30Gly	missense_variant	Exon 2 of 13	ENST00000300061.3	NP_001030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1G	ENST00000300061.3	c.88C>G	p.Arg30Gly	missense_variant	Exon 2 of 13	1	NM_001039.4	ENSP00000300061.2
ENSG00000285613	ENST00000648673.1	n.37G>C		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461854 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Bronchiectasis with or without elevated sweat chloride 3;C4748251:Liddle syndrome 2;C5774256:Pseudohypoaldosteronism, type IB3, autosomal recessive Uncertain:1

Jun 19, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.21	B
Vest4		0.52
MVP		0.57
MPC		1.6
ClinPred		0.084	T
GERP RS		3.4
Varity_R		0.12
gMVP		0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs373976756; hg19: chr16-23197680;