6-112100741-C-G

Variant names:

• chr6-112100741-C-G
• rs149743977
• NM_001033564.3:c.197C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033564.3(FAM229B):​c.197C>G​(p.Thr66Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,718 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T66M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM229B NM_001033564.3 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.1091038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM229B	NM_001033564.3	c.197C>G	p.Thr66Arg	missense_variant	Exon 4 of 4	ENST00000368656.7	NP_001028736.1
FAM229B	XM_017011174.3	c.197C>G	p.Thr66Arg	missense_variant	Exon 4 of 4		XP_016866663.1
FAM229B	XM_017011175.3	c.197C>G	p.Thr66Arg	missense_variant	Exon 3 of 3		XP_016866664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM229B	ENST00000368656.7	c.197C>G	p.Thr66Arg	missense_variant	Exon 4 of 4	1	NM_001033564.3	ENSP00000357645.2
FAM229B	ENST00000604268.1	c.197C>G	p.Thr66Arg	missense_variant	Exon 4 of 4	5		ENSP00000474987.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251372 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461718 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727142

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.0039	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.84	N;.
REVEL	Benign	0.058
Sift	Uncertain	0.0080	D;.
Sift4G	Benign	0.23	T;T
Polyphen		0.044	B;B
Vest4		0.29
MutPred		0.23		Loss of glycosylation at T66 (P = 0.0021);Loss of glycosylation at T66 (P = 0.0021);
MVP		0.043
MPC		0.33
ClinPred		0.83	D
GERP RS		4.0
Varity_R		0.13
gMVP		0.18

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: rs149743977; hg19: chr6-112421944;