2-96972133-C-G

Variant names:

• chr2-96972133-C-G
• rs1007881524
• NM_001122646.3:c.332G>C

Variant summary

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

The NM_001122646.3(FAM178B):​c.332G>C​(p.Ser111Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,379,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. S111N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FAM178B NM_001122646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03
• Publications: 0 publications found

Genes affected

FAM178B (HGNC:28036): (family with sequence similarity 178 member B)

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=0.23919299).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122646.3. 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
	FAM178B	NM_001122646.3	MANE Select	c.332G>C	p.Ser111Thr	missense	Exon 3 of 17	NP_001116118.2	Q8IXR5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM178B	ENST00000490605.3	TSL:5 MANE Select	c.332G>C	p.Ser111Thr	missense	Exon 3 of 17	ENSP00000429896.1	Q8IXR5-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000751 AC: 1 AN: 133146 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000202

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1379782 Hom.: 0 Cov.: 30 AF XY: 0.00000294 AC XY: 2 AN XY: 679152

African (AFR) AF: 0.00 AC: 0 AN: 30950

American (AMR) AF: 0.00 AC: 0 AN: 33034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23644

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35602

South Asian (SAS) AF: 0.00 AC: 0 AN: 76454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5546

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069706

Other (OTH) AF: 0.0000175 AC: 1 AN: 57132

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	0.093
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.92	T
PhyloP100		3.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.21
MVP		0.51
MPC		0.36
ClinPred		0.69	D
GERP RS		4.2
gMVP		0.082
Mutation Taster		=94/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1007881524; hg19: chr2-97637870;