11-95789429-G-T

Variant names:

• chr11-95789429-G-T
• rs750474535
• NM_144664.5:c.50C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_144664.5(FAM76B):​c.50C>A​(p.Pro17His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,609,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM76B NM_144664.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40

Genes affected

FAM76B (HGNC:28492): (family with sequence similarity 76 member B) Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM76B	NM_144664.5	c.50C>A	p.Pro17His	missense_variant	Exon 1 of 10	ENST00000358780.10	NP_653265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM76B	ENST00000358780.10	c.50C>A	p.Pro17His	missense_variant	Exon 1 of 10	1	NM_144664.5	ENSP00000351631.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457250 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724586

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

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: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.76
MutPred		0.38		Loss of glycosylation at P17 (P = 0.0519);Loss of glycosylation at P17 (P = 0.0519);
MVP		0.75
MPC		1.0
ClinPred		1.0	D
GERP RS		4.0
Varity_R		0.90
gMVP		0.60

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: rs750474535; hg19: chr11-95522593;