1-166070357-T-C

Variant names:

• chr1-166070357-T-C
• NM_001017961.5:c.670A>G

Variant summary

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

The NM_001017961.5(FAM78B):​c.670A>G​(p.Ser224Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

Genes affected

FAM78B (HGNC:13495): (family with sequence similarity 78 member B)

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=0.101411104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78B	NM_001017961.5	c.670A>G	p.Ser224Gly	missense_variant	Exon 2 of 2	ENST00000354422.4	NP_001017961.1
FAM78B	NM_001320302.2	c.264-9694A>G		intron_variant	Intron 1 of 1		NP_001307231.1
FAM78B	NR_135199.2	n.1423A>G		non_coding_transcript_exon_variant	Exon 2 of 3
FAM78B	NR_163271.1	n.1177A>G		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM78B	ENST00000354422.4	c.670A>G	p.Ser224Gly	missense_variant	Exon 2 of 2	2	NM_001017961.5	ENSP00000346404.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670A>G (p.S224G) alteration is located in exon 2 (coding exon 2) of the FAM78B gene. This alteration results from a A to G substitution at nucleotide position 670, causing the serine (S) at amino acid position 224 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.084
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.52	N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.040
Sift	Benign	0.39	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.034	B;B
Vest4		0.10
MutPred		0.14		Loss of phosphorylation at S224 (P = 0.0196);Loss of phosphorylation at S224 (P = 0.0196);
MVP		0.068
MPC		0.61
ClinPred		0.74	D
GERP RS		4.5
Varity_R		0.15
gMVP		0.082

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-166039594;