chr1-27749133-C-T

Variant names:

• chr1-27749133-C-T
• NM_152660.3:c.578C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152660.3(FAM76A):​c.578C>T​(p.Ser193Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FAM76A NM_152660.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 publications found

Genes affected

FAM76A (HGNC:28530): (family with sequence similarity 76 member A) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152660.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76A	NM_152660.3	MANE Select	c.578C>T	p.Ser193Leu	missense	Exon 6 of 9	NP_689873.1	Q8TAV0-1
	FAM76A	NM_001143912.2		c.680C>T	p.Ser227Leu	missense	Exon 7 of 10	NP_001137384.1	Q8TAV0-3
	FAM76A	NM_001143913.2		c.614+4322C>T		intron	N/A	NP_001137385.1	Q8TAV0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM76A	ENST00000373954.11	TSL:1 MANE Select	c.578C>T	p.Ser193Leu	missense	Exon 6 of 9	ENSP00000363065.5	Q8TAV0-1
	FAM76A	ENST00000010299.10	TSL:1	c.680C>T	p.Ser227Leu	missense	Exon 7 of 10	ENSP00000010299.6	Q8TAV0-3
	FAM76A	ENST00000530324.5	TSL:1	c.578C>T	p.Ser193Leu	missense	Exon 6 of 8	ENSP00000436176.1	E9PQL1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.069
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.042
Sift	Benign	0.48	T
Sift4G	Benign	0.077	T
Polyphen		0.0	B
Vest4		0.076
MutPred		0.32		Gain of sheet (P = 0.0266)
MVP		0.51
MPC		0.63
ClinPred		0.59	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.57
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.31		Position offset: 21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-28075644;