10-87020370-C-A

Variant names:

• chr10-87020370-C-A
• rs767968466
• NM_001146157.3:c.46C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146157.3(FAM25A):​c.46C>A​(p.Arg16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,172 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. 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. R16H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM25A NM_001146157.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29831177).

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.46C>A	p.Arg16Ser	missense	Exon 1 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.46C>A	p.Arg16Ser	missense	Exon 1 of 3	ENSP00000342790.4	B3EWG3
	ENSG00000151303	ENST00000444180.3	TSL:2	n.984-1944C>A		intron	N/A
	ENSG00000293605	ENST00000715806.1		n.662-4171C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 153638 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1397172 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 689118

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31524

American (AMR) AF: 0.00 AC: 0 AN: 35696

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4068

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078798

Other (OTH) AF: 0.00 AC: 0 AN: 57814

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.76	T
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.4	N
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.013	D
Vest4		0.49
MVP		0.18
ClinPred		0.39	T
GERP RS		2.4
PromoterAI		0.021	Neutral
Varity_R		0.098
gMVP		0.37
Mutation Taster		=97/3	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

dbSNP: rs767968466; hg19: chr10-88780127;