Genetic Variant FAM161B:p.Val644Leu (chr14-73934270-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_152445.3(FAM161B):c.1930G>C(p.Val644Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,611,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

FAM161B
NM_152445.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.316

Publications

0 publications found

Variant links:

Genes affected

FAM161B (HGNC:19854): (FAM161 centrosomal protein B) Predicted to be involved in cilium organization. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

FAM161B links:

ENSG00000258891 (HGNC:):

ENSG00000258891 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04684055).

BP6

Variant 14-73934270-C-G is Benign according to our data. Variant chr14-73934270-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2379308.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152445.3. 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
	FAM161B	NM_152445.3	MANE Select	c.1930G>C	p.Val644Leu	missense	Exon 9 of 9	NP_689658.3	Q96MY7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM161B	ENST00000286544.5	TSL:1 MANE Select	c.1930G>C	p.Val644Leu	missense	Exon 9 of 9	ENSP00000286544.4	Q96MY7-1
ENSG00000258891	ENST00000555916.1	TSL:1	n.407+1679G>C		intron	N/A
FAM161B	ENST00000651776.1		c.2119G>C	p.Val707Leu	missense	Exon 9 of 9	ENSP00000499021.1	Q96MY7-2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00

GnomAD2 exomes

AF:

0.0000481

AC:

AN:

249356

AF XY:

0.0000519

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

190

AN:

1458962

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

725818

show subpopulations

African (AFR)

AF:

0.0000900

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

44056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

85962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000157

AC:

175

AN:

1111438

Other (OTH)

AF:

0.000199

AC:

AN:

60184

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

AF:

0.000118

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3340

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000106

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

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

0.087

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

(source)

DANN

Benign

0.44

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.23

M_CAP

Benign

0.0022

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.97

PhyloP100

0.32

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.50

REVEL

Benign

0.036

Sift

Benign

0.25

Sift4G

Benign

0.20

Vest4

0.017

MVP

0.11

MPC

0.061

ClinPred

0.035

GERP RS

-2.8

Mutation Taster

=99/1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over