chr13-42784079-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001318932.2(FAM216B):​c.12C>A​(p.Asn4Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,450,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

FAM216B
NM_001318932.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.213
Variant links:
Genes affected
FAM216B (HGNC:26883): (family with sequence similarity 216 member B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0373511).
BP6
Variant 13-42784079-C-A is Benign according to our data. Variant chr13-42784079-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2601091.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FAM216BNM_001318932.2 linkc.12C>A p.Asn4Lys missense_variant Exon 2 of 4 ENST00000313851.3 NP_001305861.1 Q8N7L0
FAM216BNM_182508.3 linkc.12C>A p.Asn4Lys missense_variant Exon 2 of 4 NP_872314.1 Q8N7L0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FAM216BENST00000313851.3 linkc.12C>A p.Asn4Lys missense_variant Exon 2 of 4 1 NM_001318932.2 ENSP00000319336.1 Q8N7L0
FAM216BENST00000537894.5 linkc.12C>A p.Asn4Lys missense_variant Exon 2 of 4 4 ENSP00000445786.1 Q8N7L0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000203
AC:
5
AN:
246856
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133488
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000601
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000689
AC:
10
AN:
1450508
Hom.:
0
Cov.:
33
AF XY:
0.00000832
AC XY:
6
AN XY:
721552
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000115
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000361
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000225
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Aug 22, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.95
DANN
Benign
0.088
DEOGEN2
Benign
0.0054
T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.35
T;.
M_CAP
Benign
0.0034
T
MetaRNN
Benign
0.037
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-0.59
N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.059
Sift
Benign
0.68
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
B;B
Vest4
0.046
MutPred
0.26
Gain of methylation at N4 (P = 0.003);Gain of methylation at N4 (P = 0.003);
MVP
0.030
MPC
0.042
ClinPred
0.019
T
GERP RS
2.0
Varity_R
0.034
gMVP
0.029

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

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

Other links and lift over

dbSNP: rs777435097; hg19: chr13-43358215; API