2-96970765-C-T

Variant names:

• chr2-96970765-C-T
• rs757675684
• NM_001122646.3:c.577G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122646.3(FAM178B):​c.577G>A​(p.Gly193Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,550,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 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. G193C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000044 (0 hom.)
• Consequence: FAM178B NM_001122646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056560725).

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.577G>A	p.Gly193Ser	missense	Exon 4 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.577G>A	p.Gly193Ser	missense	Exon 4 of 17	ENSP00000429896.1	Q8IXR5-3

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151932 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000121

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000325 AC: 5 AN: 153986 AF XY: 0.0000490

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: 0.0000655

Gnomad NFE exome AF: 0.0000503

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000443 AC: 62 AN: 1398876 Hom.: 0 Cov.: 30 AF XY: 0.0000507 AC XY: 35 AN XY: 689994

African (AFR) AF: 0.0000317 AC: 1 AN: 31588

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.0000794 AC: 2 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79222

European-Finnish (FIN) AF: 0.0000406 AC: 2 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000491 AC: 53 AN: 1078530

Other (OTH) AF: 0.0000173 AC: 1 AN: 57970

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151932 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74160

African (AFR) AF: 0.000121 AC: 5 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000814 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.1
DANN	Benign	0.76
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.93
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.025
Sift	Benign	0.51	T
Sift4G	Benign	0.48	T
Vest4		0.13
MVP		0.24
MPC		0.067
ClinPred		0.041	T
GERP RS		-2.6
gMVP		0.035
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs757675684; hg19: chr2-97636502;