chr2-96877988-G-C

Variant names:

• chr2-96877988-G-C
• rs371471695
• NM_001122646.3:c.1909C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001122646.3(FAM178B):​c.1909C>G​(p.Arg637Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,934 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R637W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM178B NM_001122646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

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.1909C>G	p.Arg637Gly	missense	Exon 16 of 17	NP_001116118.2	Q8IXR5-3
	FAM178B	NM_001172667.2		c.286C>G	p.Arg96Gly	missense	Exon 4 of 5	NP_001166138.1	Q8IXR5-4
	FAM178B	NM_016490.5		c.229C>G	p.Arg77Gly	missense	Exon 4 of 5	NP_057574.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM178B	ENST00000490605.3	TSL:5 MANE Select	c.1909C>G	p.Arg637Gly	missense	Exon 16 of 17	ENSP00000429896.1	Q8IXR5-3
	FAM178B	ENST00000393526.6	TSL:1	c.229C>G	p.Arg77Gly	missense	Exon 4 of 5	ENSP00000377160.2	Q8IXR5-2
	FAM178B	ENST00000470789.5	TSL:1	n.341C>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460934 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726828

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.26	T
PhyloP100		4.6
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Vest4		0.63
MVP		0.59
MPC		0.43
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
gMVP		0.43
Mutation Taster		=86/14	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

dbSNP: rs371471695; hg19: chr2-97543725;