6-112099378-C-T

Variant names:

• chr6-112099378-C-T
• rs1262639539
• NM_001033564.3:c.95C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: FAM229B NM_001033564.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

Genes affected

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

ACMG classification

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 rank	MANE	Protein	UniProt
FAM229B	NM_001033564.3	c.95C>T	p.Ala32Val	missense_variant	Exon 3 of 4	ENST00000368656.7	NP_001028736.1
FAM229B	XM_017011174.3	c.95C>T	p.Ala32Val	missense_variant	Exon 3 of 4		XP_016866663.1
FAM229B	XM_017011175.3	c.95C>T	p.Ala32Val	missense_variant	Exon 2 of 3		XP_016866664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM229B	ENST00000368656.7	c.95C>T	p.Ala32Val	missense_variant	Exon 3 of 4	1	NM_001033564.3	ENSP00000357645.2
FAM229B	ENST00000604268.1	c.95C>T	p.Ala32Val	missense_variant	Exon 3 of 4	5		ENSP00000474987.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 32

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.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152112 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74300

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

Submissions by phenotype

not specified Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Benign	0.90
DEOGEN2	Benign	0.0070	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.015
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.62	.;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.38	T
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	T
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

Other links and lift over

dbSNP: rs1262639539; hg19: chr6-112420581;