1-166070457-C-A

Variant names:

• chr1-166070457-C-A
• NM_001017961.5:c.570G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001017961.5(FAM78B):​c.570G>T​(p.Lys190Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM78B NM_001017961.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39079827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM78B	NM_001017961.5	c.570G>T	p.Lys190Asn	missense_variant	Exon 2 of 2	ENST00000354422.4	NP_001017961.1
FAM78B	NM_001320302.2	c.264-9794G>T		intron_variant	Intron 1 of 1		NP_001307231.1
FAM78B	NR_135199.2	n.1323G>T		non_coding_transcript_exon_variant	Exon 2 of 3
FAM78B	NR_163271.1	n.1077G>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.570G>T	p.Lys190Asn	missense_variant	Exon 2 of 2	2	NM_001017961.5	ENSP00000346404.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461882 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.570G>T (p.K190N) alteration is located in exon 2 (coding exon 2) of the FAM78B gene. This alteration results from a G to T substitution at nucleotide position 570, causing the lysine (K) at amino acid position 190 to be replaced by an asparagine (N). 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	Pathogenic	0.98
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.021
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.14
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.59	P;P
Vest4		0.54
MutPred		0.34		Loss of methylation at K190 (P = 0.0191);Loss of methylation at K190 (P = 0.0191);
MVP		0.082
MPC		1.5
ClinPred		0.99	D
GERP RS		2.9
Varity_R		0.50
gMVP		0.58

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: chr1-166039694;