rs992153172

Variant names:

• chr1-166070618-T-C
• rs992153172
• NM_001017961.5:c.409A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001017961.5(FAM78B):​c.409A>G​(p.Ser137Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78B	NM_001017961.5	c.409A>G	p.Ser137Gly	missense_variant	Exon 2 of 2	ENST00000354422.4	NP_001017961.1
FAM78B	NM_001320302.2	c.264-9955A>G		intron_variant	Intron 1 of 1		NP_001307231.1
FAM78B	NR_135199.2	n.1162A>G		non_coding_transcript_exon_variant	Exon 2 of 3
FAM78B	NR_163271.1	n.916A>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.409A>G	p.Ser137Gly	missense_variant	Exon 2 of 2	2	NM_001017961.5	ENSP00000346404.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461476 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.409A>G (p.S137G) 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 409, causing the serine (S) at amino acid position 137 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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.0067	T
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D;D
REVEL	Benign	0.29
Sift	Benign	0.049	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		0.97	D;D
Vest4		0.58
MutPred		0.45		Loss of stability (P = 0.0945);Loss of stability (P = 0.0945);
MVP		0.18
MPC		0.94
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.43
gMVP		0.54

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

LitVar

Other links and lift over

dbSNP: rs992153172; hg19: chr1-166039855;