rs9558965

Variant names:

• chr13-107183289-C-T
• rs9558965
• NM_001080396.3:c.1088-12503G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080396.3(NALF1):​c.1088-12503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,200 control chromosomes in the GnomAD database, including 562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (562 hom., cov: 33)
• Consequence: NALF1 NM_001080396.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALF1	NM_001080396.3	c.1088-12503G>A		intron_variant	Intron 2 of 2	ENST00000375915.4	NP_001073865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NALF1	ENST00000375915.4	c.1088-12503G>A		intron_variant	Intron 2 of 2	1	NM_001080396.3	ENSP00000365080.1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12692 AN: 152082 Hom.: 561 Cov.: 33

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0577

Gnomad ASJ AF: 0.0669

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0834 AC: 12690 AN: 152200 Hom.: 562 Cov.: 33 AF XY: 0.0853 AC XY: 6349 AN XY: 74400

African (AFR) AF: 0.123 AC: 5108 AN: 41520

American (AMR) AF: 0.0575 AC: 880 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0669 AC: 232 AN: 3470

East Asian (EAS) AF: 0.121 AC: 623 AN: 5160

South Asian (SAS) AF: 0.113 AC: 544 AN: 4822

European-Finnish (FIN) AF: 0.0885 AC: 938 AN: 10602

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4118 AN: 68018

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0706 Hom.: 822

Bravo AF: 0.0813

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.49
DANN	Benign	0.68
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9558965; hg19: chr13-107835637;