Genetic Variant FAM216B:p.Asn4Lys (chr13-42784079-C-A) – ACMG Classification: Likely_benign (-4 pts)

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

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)

FAM216B links:

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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
FAM216B	NM_001318932.2 link	c.12C>A	p.Asn4Lys	missense_variant	Exon 2 of 4	ENST00000313851.3	NP_001305861.1	Q8N7L0
FAM216B	NM_182508.3 link	c.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
FAM216B	ENST00000313851.3 link	c.12C>A	p.Asn4Lys	missense_variant	Exon 2 of 4	1	NM_001318932.2	ENSP00000319336.1		Q8N7L0
FAM216B	ENST00000537894.5 link	c.12C>A	p.Asn4Lys	missense_variant	Exon 2 of 4	4		ENSP00000445786.1		Q8N7L0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

246856

Hom.:

AF XY:

0.0000150

AC XY:

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:

AN:

1450508

Hom.:

Cov.:

AF XY:

0.00000832

AC XY:

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.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

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

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

LIST_S2

Benign

0.35

T;.

M_CAP

Benign

0.0034

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.59

N;N

PrimateAI

Benign

0.32

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over