rs1184323456

Variant names:

• chr1-166070289-C-A
• NM_001017961.5:c.738G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-166070289-C-A
• chr1-166070289-C-T

Variant summary

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

The NM_001017961.5(FAM78B):​c.738G>T​(p.Met246Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,292 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.80

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78B	NM_001017961.5	c.738G>T	p.Met246Ile	missense_variant	Exon 2 of 2	ENST00000354422.4	NP_001017961.1
FAM78B	NM_001320302.2	c.264-9626G>T		intron_variant	Intron 1 of 1		NP_001307231.1
FAM78B	NR_135199.2	n.1491G>T		non_coding_transcript_exon_variant	Exon 2 of 3
FAM78B	NR_163271.1	n.1245G>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.738G>T	p.Met246Ile	missense_variant	Exon 2 of 2	2	NM_001017961.5	ENSP00000346404.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418292 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 699626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T;T
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.6	L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.56	N;N
REVEL	Uncertain	0.60
Sift	Benign	0.72	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.91	P;P
Vest4		0.80
MutPred		0.37		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.99
MPC		1.7
ClinPred		0.93	D
GERP RS		6.0
Varity_R		0.24
gMVP		0.36

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: chr1-166039526;