12-6346853-CAACA-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001038.6(SCNN1A):c.*1016_*1019del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 152,154 control chromosomes in the GnomAD database, including 309 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (309 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCNN1A NM_001038.6 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.34

Genes affected

SCNN1A (HGNC:10599): (sodium channel epithelial 1 subunit alpha) 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 alpha subunit, and mutations in this gene have been associated with pseudohypoaldosteronism type 1 (PHA1), a rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2009]

LOC112268088 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-6346853-CAACA-C is Benign according to our data. Variant chr12-6346853-CAACA-C is described in ClinVar as [Likely_benign]. Clinvar id is 310117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCNN1A	NM_001038.6	c.*1016_*1019del		3_prime_UTR_variant	13/13	ENST00000228916.7
LOC112268088	XR_002957396.2	n.707_710del		non_coding_transcript_exon_variant	2/2
SCNN1A	NM_001159575.2	c.*1016_*1019del		3_prime_UTR_variant	13/13
SCNN1A	NM_001159576.2	c.*1016_*1019del		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCNN1A	ENST00000228916.7	c.*1016_*1019del		3_prime_UTR_variant	13/13	1	NM_001038.6	A2
SCNN1A	ENST00000360168.7	c.*1016_*1019del		3_prime_UTR_variant	12/12	1		A2
SCNN1A	ENST00000540037.5	c.*1016_*1019del		3_prime_UTR_variant	11/11	1

Frequencies

GnomAD3 genomes AF: 0.0362 AC: 5502 AN: 152036 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0124

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0274

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 490 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 306

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0364 AC: 5535 AN: 152154 Hom.: 309 Cov.: 32 AF XY: 0.0357 AC XY: 2658 AN XY: 74376

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0271

Alfa AF: 0.0272 Hom.: 20

Bravo AF: 0.0415

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

- -

Autosomal recessive pseudohypoaldosteronism type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bronchiectasis with or without elevated sweat chloride 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial Periodic Fever Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs796798913; hg19: chr12-6456019;