Variant 6-112099378-C-T 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.95C>T(p.Ala32Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

FAM229B
NM_001033564.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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=0.08225337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM229B	NM_001033564.3 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	3/4	ENST00000368656.7	NP_001028736.1	Q4G0N7
FAM229B	XM_017011174.3 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	3/4		XP_016866663.1	Q4G0N7
FAM229B	XM_017011175.3 linkuse as main transcript	c.95C>T	p.Ala32Val	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.95C>T	p.Ala32Val	missense_variant	3/4	1	NM_001033564.3	ENSP00000357645.2		Q4G0N7
FAM229B	ENST00000604268.1 linkuse as main transcript	c.95C>T	p.Ala32Val	missense_variant	3/4	5		ENSP00000474987.1		Q4G0N7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Oct 11, 2024

The c.95C>T (p.A32V) alteration is located in exon 3 (coding exon 1) of the FAM229B gene. This alteration results from a C to T substitution at nucleotide position 95, causing the alanine (A) at amino acid position 32 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0070

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.015

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.62

.;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.4

N;.

REVEL

Benign

0.029

Sift

Benign

0.061

T;.

Sift4G

Benign

0.15

T;T

Polyphen

0.042

B;B

Vest4

0.18

MutPred

0.16

Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);

MVP

0.082

MPC

0.29

ClinPred

0.45

GERP RS

4.3

Varity_R

0.061

gMVP

0.13

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