13-107170569-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001080396.3(NALF1):c.1305A>G(p.Ala435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,614,176 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (28 hom.)
• Consequence: NALF1 NM_001080396.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.610

Genes affected

NALF1 (HGNC:33877): (NALCN channel auxiliary factor 1) Predicted to contribute to stretch-activated, cation-selective, calcium channel activity. Predicted to be involved in calcium ion import across plasma membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-107170569-T-C is Benign according to our data. Variant chr13-107170569-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2643928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.61 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NALF1	NM_001080396.3	c.1305A>G	p.Ala435=	synonymous_variant	3/3	ENST00000375915.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NALF1	ENST00000375915.4	c.1305A>G	p.Ala435=	synonymous_variant	3/3	1	NM_001080396.3	P1

Frequencies

GnomAD3 genomes AF: 0.00396 AC: 603 AN: 152216 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00394

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00426 AC: 1070 AN: 251422 Hom.: 4 AF XY: 0.00458 AC XY: 623 AN XY: 135886

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.0242

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00542

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.00428

Gnomad OTH exome AF: 0.00897

GnomAD4 exome AF: 0.00378 AC: 5528 AN: 1461842 Hom.: 28 Cov.: 31 AF XY: 0.00391 AC XY: 2844 AN XY: 727226

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00320

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00588

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00344

Gnomad4 OTH exome AF: 0.00513

GnomAD4 genome AF: 0.00396 AC: 603 AN: 152334 Hom.: 6 Cov.: 33 AF XY: 0.00400 AC XY: 298 AN XY: 74486

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00394

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00490 Hom.: 1

Bravo AF: 0.00457

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.00632

EpiControl AF: 0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

NALF1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.038
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs141380144; hg19: chr13-107822917;