Variant 9-35825612-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000423537.7(FAM221B):c.550G>A(p.Asp184Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FAM221B
ENST00000423537.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.694

Variant links:

Genes affected

FAM221B (HGNC:30762): (family with sequence similarity 221 member B)

FAM221B links:

TMEM8B (HGNC:21427): (transmembrane protein 8B) Involved in cell-matrix adhesion. Located in cell surface and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM8B 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=0.049963653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM221B	NM_001012446.4 linkuse as main transcript	c.550G>A	p.Asp184Asn	missense_variant	2/7	ENST00000423537.7	NP_001012448.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM221B	ENST00000423537.7 linkuse as main transcript	c.550G>A	p.Asp184Asn	missense_variant	2/7	1	NM_001012446.4	ENSP00000415299	P1	A6H8Z2-1
FAM221B	ENST00000377984.2 linkuse as main transcript	c.550G>A	p.Asp184Asn	missense_variant	3/6	1		ENSP00000367222
FAM221B	ENST00000388950.8 linkuse as main transcript	c.550G>A	p.Asp184Asn	missense_variant, NMD_transcript_variant	2/8	1		ENSP00000373602		A6H8Z2-3
TMEM8B	ENST00000377996.5 linkuse as main transcript	c.-451+9378C>T		intron_variant		2		ENSP00000367235		A6NDV4-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249342

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135280

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000252

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000165

AC:

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

May 20, 2024

The c.550G>A (p.D184N) alteration is located in exon 2 (coding exon 1) of the FAM221B gene. This alteration results from a G to A substitution at nucleotide position 550, causing the aspartic acid (D) at amino acid position 184 to be replaced by an asparagine (N). 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

0.087

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

T;.

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.024

Sift

Benign

0.46

T;T

Sift4G

Benign

0.45

T;.

Polyphen

0.0090

B;.

Vest4

0.088

MVP

0.048

MPC

0.069

ClinPred

0.042

GERP RS

2.9

Varity_R

0.037

gMVP

0.083

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