Genetic Variant NM_152445.3:c.1806G>T (chr14-73934394-C-A) – 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.1806G>T(p.Arg602Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000277 in 1,589,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

FAM161B
NM_152445.3 missense, splice_region

Scores

Splicing: ADA: 0.3627

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.684

Publications

1 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=0.017201334).

BP6

Variant 14-73934394-C-A is Benign according to our data. Variant chr14-73934394-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2513112.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.1806G>T	p.Arg602Ser	missense splice_region	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.1806G>T	p.Arg602Ser	missense splice_region	Exon 9 of 9	ENSP00000286544.4	Q96MY7-1
ENSG00000258891	ENST00000555916.1	TSL:1	n.407+1555G>T		intron	N/A
FAM161B	ENST00000651776.1		c.1995G>T	p.Arg665Ser	missense splice_region	Exon 9 of 9	ENSP00000499021.1	Q96MY7-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000484

AC:

AN:

227324

AF XY:

0.0000405

show subpopulations

Gnomad AFR exome

AF:

0.000190

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:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1437790

Hom.:

Cov.:

AF XY:

0.0000336

AC XY:

AN XY:

715322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31552

American (AMR)

AF:

0.00

AC:

AN:

36046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24780

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.000207

AC:

AN:

82012

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

1105938

Other (OTH)

AF:

0.0000338

AC:

AN:

59240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

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:

0.0000395

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000452

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

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

-0.74

CADD

Benign

(source)

DANN

Benign

0.70

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.28

M_CAP

Benign

0.0018

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.94

PhyloP100

0.68

PrimateAI

Benign

0.23

PROVEAN

Benign

2.2

REVEL

Benign

0.015

Sift

Benign

0.57

Sift4G

Benign

0.57

Vest4

0.069

MVP

0.040

MPC

0.070

ClinPred

0.0048

GERP RS

1.7

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.36

dbscSNV1_RF

Benign

0.47

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.20

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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