rs370799481

Variant names:

• chr5-74781912-T-C
• NM_001376049.1:c.1561A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-74781912-T-C
• chr5-74781912-T-G

Variant summary

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

The NM_001376049.1(FAM169A):​c.1561A>G​(p.Lys521Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. K521Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM169A NM_001376049.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.69

Genes affected

FAM169A (HGNC:29138): (family with sequence similarity 169 member A) Predicted to be located in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.15897405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM169A	NM_001376049.1	c.1561A>G	p.Lys521Glu	missense_variant	Exon 13 of 13	ENST00000687041.1	NP_001362978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM169A	ENST00000687041.1	c.1561A>G	p.Lys521Glu	missense_variant	Exon 13 of 13		NM_001376049.1	ENSP00000508577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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	Benign	0.11
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.17
Sift	Benign	0.090	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.99	D;D
Vest4		0.33
MutPred		0.26		Loss of ubiquitination at K521 (P = 0.0037);.;
MVP		0.043
MPC		1.0
ClinPred		0.57	D
GERP RS		6.0
Varity_R		0.21
gMVP		0.11

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: chr5-74077737;