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

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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

Publications

0 publications found

Variant links:

Genes affected

FAM216B (HGNC:26883): (family with sequence similarity 216 member B)

FAM216B links:

ENSG00000304100 (HGNC:):

ENSG00000304100 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2601091.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318932.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM216B	NM_001318932.2	MANE Select	c.12C>A	p.Asn4Lys	missense	Exon 2 of 4	NP_001305861.1	Q8N7L0
	FAM216B	NM_182508.3		c.12C>A	p.Asn4Lys	missense	Exon 2 of 4	NP_872314.1	Q8N7L0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM216B	ENST00000313851.3	TSL:1 MANE Select	c.12C>A	p.Asn4Lys	missense	Exon 2 of 4	ENSP00000319336.1	Q8N7L0
FAM216B	ENST00000537894.5	TSL:4	c.12C>A	p.Asn4Lys	missense	Exon 2 of 4	ENSP00000445786.1	Q8N7L0
ENSG00000304100	ENST00000799675.1		n.139-779G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000203

AC:

AN:

246856

AF XY:

0.0000150

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 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

African (AFR)

AF:

0.00

AC:

AN:

32812

American (AMR)

AF:

0.000115

AC:

AN:

43340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25752

East Asian (EAS)

AF:

0.00

AC:

AN:

39448

South Asian (SAS)

AF:

0.00

AC:

AN:

84362

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

1106536

Other (OTH)

AF:

0.0000167

AC:

AN:

59772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.95

(source)

DANN

Benign

0.088

DEOGEN2

Benign

0.0054

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.35

M_CAP

Benign

0.0034

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.59

PhyloP100

0.21

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

REVEL

Benign

0.059

Sift

Benign

0.68

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.046

MutPred

0.26

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

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over