Genetic Variant SCNN1D:p.Pro175Pro (chr1-1285631-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001130413.4(SCNN1D):c.525C>A(p.Pro175Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,547,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

SCNN1D
NM_001130413.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.188

Variant links:

Genes affected

SCNN1D (HGNC:10601): (sodium channel epithelial 1 subunit delta) Predicted to enable ligand-gated sodium channel activity. Predicted to be involved in sodium ion transmembrane transport. Located in actin cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SCNN1D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.005).

BP6

Variant 1-1285631-C-A is Benign according to our data. Variant chr1-1285631-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2672317.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-1285631-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.188 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCNN1D	NM_001130413.4 link	c.525C>A	p.Pro175Pro	synonymous_variant	Exon 6 of 18	ENST00000379116.10	NP_001123885.2	P51172-3
SCNN1D	NR_037668.3 link	n.691-295C>A		intron_variant	Intron 5 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCNN1D	ENST00000379116.10 link	c.525C>A	p.Pro175Pro	synonymous_variant	Exon 6 of 18	5	NM_001130413.4	ENSP00000368411.5		P51172-3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000245

AC:

AN:

150832

AF XY:

0.000262

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00177

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.000235

GnomAD4 exome

AF:

0.000211

AC:

294

AN:

1395254

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

146

AN XY:

687972

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

31520

Gnomad4 AMR exome

AF:

0.0000284

AC:

AN:

35190

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25036

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

35710

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

78868

Gnomad4 FIN exome

AF:

0.00223

AC:

107

AN:

47910

Gnomad4 NFE exome

AF:

0.000162

AC:

175

AN:

1077498

Gnomad4 Remaining exome

AF:

0.000190

AC:

AN:

57846

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00132

AC:

0.00131703

AN:

0.00131703

Gnomad4 NFE

AF:

0.000118

AC:

0.000117581

AN:

0.000117581

Gnomad4 OTH

AF:

0.000478

AC:

0.000478469

AN:

0.000478469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.0000869

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SCNN1D: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.3

DANN

Benign

0.69

Mutation Taster

=100/0

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over