13-107170625-G-A

Position:

• chr13-107170625-G-A

Variant summary

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

The NM_001080396.3(NALF1):​c.1249C>T​(p.Leu417Phe) variant causes a missense change involving the alteration of a 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NALF1 NM_001080396.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.19

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 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	Protein	UniProt
NALF1	NM_001080396.3	c.1249C>T	p.Leu417Phe	missense_variant	3/3	ENST00000375915.4	NP_001073865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NALF1	ENST00000375915.4	c.1249C>T	p.Leu417Phe	missense_variant	3/3	1	NM_001080396.3	ENSP00000365080.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.1249C>T (p.L417F) alteration is located in exon 3 (coding exon 3) of the FAM155A gene. This alteration results from a C to T substitution at nucleotide position 1249, causing the leucine (L) at amino acid position 417 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.049	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.79
MutPred		0.29		Gain of sheet (P = 0.0125);
MVP		0.12
MPC		1.3
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.70

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: rs1335944451; hg19: chr13-107822973;