rs146248661

Variant names:

• chr1-166070365-C-A
• rs146248661
• NM_001017961.5:c.662G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-166070365-C-A
• chr1-166070365-C-T

Variant summary

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

The NM_001017961.5(FAM78B):​c.662G>T​(p.Arg221Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. R221Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48

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=0.09053147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78B	NM_001017961.5	c.662G>T	p.Arg221Leu	missense_variant	Exon 2 of 2	ENST00000354422.4	NP_001017961.1
FAM78B	NM_001320302.2	c.264-9702G>T		intron_variant	Intron 1 of 1		NP_001307231.1
FAM78B	NR_135199.2	n.1415G>T		non_coding_transcript_exon_variant	Exon 2 of 3
FAM78B	NR_163271.1	n.1169G>T		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.662G>T	p.Arg221Leu	missense_variant	Exon 2 of 2	2	NM_001017961.5	ENSP00000346404.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000798 AC: 2 AN: 250582 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135370

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461270 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726862

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.045
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.048
Sift	Benign	0.80	T;T
Sift4G	Benign	0.38	T;T
Polyphen		0.0010	B;B
Vest4		0.21
MutPred		0.29		Loss of MoRF binding (P = 0.0024);Loss of MoRF binding (P = 0.0024);
MVP		0.043
MPC		1.0
ClinPred		0.23	T
GERP RS		4.6
Varity_R		0.23
gMVP		0.44

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: rs146248661; hg19: chr1-166039602;