13-107865998-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001080396.3(NALF1):​c.599C>T​(p.Ala200Val) variant causes a missense change. The variant allele was found at a frequency of 0.00008 in 1,611,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

NALF1
NM_001080396.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12405598).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NALF1NM_001080396.3 linkuse as main transcriptc.599C>T p.Ala200Val missense_variant 1/3 ENST00000375915.4 NP_001073865.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NALF1ENST00000375915.4 linkuse as main transcriptc.599C>T p.Ala200Val missense_variant 1/31 NM_001080396.3 ENSP00000365080 P1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152128
Hom.:
0
Cov.:
31
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000221
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000926
AC:
23
AN:
248482
Hom.:
0
AF XY:
0.0000741
AC XY:
10
AN XY:
134884
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000490
Gnomad NFE exome
AF:
0.000178
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000774
AC:
113
AN:
1459718
Hom.:
0
Cov.:
33
AF XY:
0.0000881
AC XY:
64
AN XY:
726288
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000389
Gnomad4 NFE exome
AF:
0.0000962
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152128
Hom.:
0
Cov.:
31
AF XY:
0.000108
AC XY:
8
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000201
Hom.:
0
Bravo
AF:
0.0000869
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 06, 2023The c.599C>T (p.A200V) alteration is located in exon 1 (coding exon 1) of the FAM155A gene. This alteration results from a C to T substitution at nucleotide position 599, causing the alanine (A) at amino acid position 200 to be replaced by a valine (V). 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
0.10
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.56
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.51
T
M_CAP
Benign
0.033
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.095
Sift
Benign
0.076
T
Sift4G
Benign
0.27
T
Polyphen
0.28
B
Vest4
0.29
MVP
0.043
MPC
1.1
ClinPred
0.063
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.9
Varity_R
0.096
gMVP
0.44

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.

Other links and lift over

dbSNP: rs202196215; hg19: chr13-108518346; API