11-95778879-C-T

Variant names:

• chr11-95778879-C-T
• NM_144664.5:c.771G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144664.5(FAM76B):​c.771G>A​(p.Met257Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,459,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FAM76B NM_144664.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23797387).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144664.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76B	NM_144664.5	MANE Select	c.771G>A	p.Met257Ile	missense	Exon 8 of 10	NP_653265.3
	FAM76B	NM_001330357.2		c.768G>A	p.Met256Ile	missense	Exon 8 of 10	NP_001317286.1	F5GX09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76B	ENST00000358780.10	TSL:1 MANE Select	c.771G>A	p.Met257Ile	missense	Exon 8 of 10	ENSP00000351631.5	Q5HYJ3-1
	FAM76B	ENST00000398187.6	TSL:1	n.*127G>A		non_coding_transcript_exon	Exon 9 of 11	ENSP00000381248.2	Q5HYJ3-3
	FAM76B	ENST00000543641.5	TSL:1	n.*127G>A		non_coding_transcript_exon	Exon 9 of 12	ENSP00000444087.1	Q5HYJ3-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459270 Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7 AN XY: 725982

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53260

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1110436

Other (OTH) AF: 0.00 AC: 0 AN: 60228

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.00038	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.030
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.060
Sift	Benign	0.042	D
Sift4G	Uncertain	0.032	D
Polyphen		0.035	B
Vest4		0.54
MutPred		0.24		Gain of ubiquitination at K260 (P = 0.0619)
MVP		0.49
MPC		0.31
ClinPred		0.66	D
GERP RS		5.0
Varity_R		0.27
gMVP		0.17
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr11-95512043;