Variant 14-73944422-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152445.3(FAM161B):c.838A>G(p.Thr280Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000378 in 1,612,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

FAM161B
NM_152445.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.127

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0036953092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM161B	NM_152445.3 linkuse as main transcript	c.838A>G	p.Thr280Ala	missense_variant	3/9	ENST00000286544.5
FAM161B	XM_011536475.3 linkuse as main transcript	c.838A>G	p.Thr280Ala	missense_variant	3/10
FAM161B	XR_007063990.1 linkuse as main transcript	n.906A>G		non_coding_transcript_exon_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM161B	ENST00000286544.5 linkuse as main transcript	c.838A>G	p.Thr280Ala	missense_variant	3/9	1	NM_152445.3	P1	Q96MY7-1
FAM161B	ENST00000651776.1 linkuse as main transcript	c.1027A>G	p.Thr343Ala	missense_variant	3/9				Q96MY7-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251346

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000387

AC:

565

AN:

1460852

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

285

AN XY:

726468

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00563

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000323

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000289

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000525

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.1027A>G (p.T343A) alteration is located in exon 3 (coding exon 3) of the FAM161B gene. This alteration results from a A to G substitution at nucleotide position 1027, causing the threonine (T) at amino acid position 343 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.55

Cadd

Benign

5.2

Dann

Benign

0.16

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.46

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.46

REVEL

Benign

0.021

Sift

Benign

0.81

Sift4G

Benign

0.96

Vest4

0.19

MVP

0.040

MPC

0.062

ClinPred

0.033

GERP RS

-0.31

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