10-87024588-A-T

Variant names:

• chr10-87024588-A-T
• NM_001146157.3:c.184A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146157.3(FAM25A):​c.184A>T​(p.Met62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,383,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: FAM25A NM_001146157.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.588
• Publications: 0 publications found

Genes affected

FAM25A (HGNC:23436): (family with sequence similarity 25 member A)

ENSG00000151303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16573086).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146157.3. 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
	FAM25A	NM_001146157.3	MANE Select	c.184A>T	p.Met62Leu	missense	Exon 3 of 3	NP_001139629.1	B3EWG3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM25A	ENST00000343959.5	TSL:1 MANE Select	c.184A>T	p.Met62Leu	missense	Exon 3 of 3	ENSP00000342790.4	B3EWG3
	ENSG00000151303	ENST00000444180.3	TSL:2	n.1094A>T		non_coding_transcript_exon	Exon 10 of 10
	ENSG00000293605	ENST00000715806.1		n.709A>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 16 AN: 1383456 Hom.: 0 Cov.: 31 AF XY: 0.00000879 AC XY: 6 AN XY: 682622

African (AFR) AF: 0.00 AC: 0 AN: 31522

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35318

Middle Eastern (MID) AF: 0.000246 AC: 1 AN: 4070

European-Non Finnish (NFE) AF: 0.0000139 AC: 15 AN: 1078864

Other (OTH) AF: 0.00 AC: 0 AN: 57928

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	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.59
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
Sift	Benign	0.086	T
Sift4G	Benign	0.095	T
Vest4		0.16
MVP		0.085
ClinPred		0.088	T
GERP RS		2.1
Varity_R		0.10
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr10-88784345;