11-95778950-T-A

Variant names:

• chr11-95778950-T-A
• rs1351844170
• NM_144664.5:c.700A>T

Variant summary

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

The NM_144664.5(FAM76B):​c.700A>T​(p.Ile234Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,606,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM76B NM_144664.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.78

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25270092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM76B	NM_144664.5	c.700A>T	p.Ile234Leu	missense_variant	Exon 8 of 10	ENST00000358780.10	NP_653265.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM76B	ENST00000358780.10	c.700A>T	p.Ile234Leu	missense_variant	Exon 8 of 10	1	NM_144664.5	ENSP00000351631.5

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151598 Hom.: 0 Cov.: 32

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455092 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723882

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: 0.00000660 AC: 1 AN: 151598 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74026

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: 0.0000148

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	Benign	0.071
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.21
Sift	Benign	0.47	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.36	B;.
Vest4		0.53
MutPred		0.055		Gain of phosphorylation at S237 (P = 0.1676);.;
MVP		0.46
MPC		0.30
ClinPred		0.56	D
GERP RS		5.8
Varity_R		0.19
gMVP		0.098

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

Other links and lift over

dbSNP: rs1351844170; hg19: chr11-95512114;