rs61729788

Positions:

• chr16-23375747-C-A
• chr16-23375747-C-G
• chr16-23375747-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000336.3(SCNN1B):​c.1162C>A​(p.Arg388Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R388C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCNN1B NM_000336.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39

Genes affected

SCNN1B (HGNC:10600): (sodium channel epithelial 1 subunit beta) 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 beta subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), and Liddle syndrome. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1B	NM_000336.3	c.1162C>A	p.Arg388Ser	missense_variant	8/13	ENST00000343070.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1B	ENST00000343070.7	c.1162C>A	p.Arg388Ser	missense_variant	8/13	1	NM_000336.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	0.00059	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.;.
Eigen	Benign	0.096
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.9	M;.;.;.
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.067	T;D;T;T
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.060	B;.;.;.
Vest4		0.43
MutPred		0.69		Gain of glycosylation at S389 (P = 0.1702);.;.;.;
MVP		0.84
MPC		0.29
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.53
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61729788; hg19: chr16-23387068;