Variant 6-112099373-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033564.3(FAM229B):c.90T>G(p.Ser30Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

FAM229B
NM_001033564.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.739

Variant links:

Genes affected

FAM229B (HGNC:33858): (family with sequence similarity 229 member B)

FAM229B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1562595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM229B	NM_001033564.3 linkuse as main transcript	c.90T>G	p.Ser30Arg	missense_variant	3/4	ENST00000368656.7	NP_001028736.1	Q4G0N7
FAM229B	XM_017011174.3 linkuse as main transcript	c.90T>G	p.Ser30Arg	missense_variant	3/4		XP_016866663.1	Q4G0N7
FAM229B	XM_017011175.3 linkuse as main transcript	c.90T>G	p.Ser30Arg	missense_variant	2/3		XP_016866664.1	Q4G0N7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM229B	ENST00000368656.7 linkuse as main transcript	c.90T>G	p.Ser30Arg	missense_variant	3/4	1	NM_001033564.3	ENSP00000357645.2		Q4G0N7
FAM229B	ENST00000604268.1 linkuse as main transcript	c.90T>G	p.Ser30Arg	missense_variant	3/4	5		ENSP00000474987.1		Q4G0N7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251184

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135764

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727128

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:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000151

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

Dec 15, 2022

The c.90T>G (p.S30R) alteration is located in exon 3 (coding exon 1) of the FAM229B gene. This alteration results from a T to G substitution at nucleotide position 90, causing the serine (S) at amino acid position 30 to be replaced by an arginine (R). 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

0.20

BayesDel_addAF

Benign

-0.0046

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.051

T;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.7

D;.

REVEL

Benign

0.13

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.025

D;D

Polyphen

0.21

B;B

Vest4

0.31

MutPred

0.20

Gain of catalytic residue at S30 (P = 0.0148);Gain of catalytic residue at S30 (P = 0.0148);

MVP

0.32

MPC

0.28

ClinPred

0.27

GERP RS

1.4

Varity_R

0.33

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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