chr10-87020370-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001146157.3(FAM25A):​c.46C>T​(p.Arg16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,549,368 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.00023 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00027 (3 hom.)
• Consequence: FAM25A NM_001146157.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012114137).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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>T	p.Arg16Cys	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>T	p.Arg16Cys	missense	Exon 1 of 3	ENSP00000342790.4	B3EWG3
	ENSG00000151303	ENST00000444180.3	TSL:2	n.984-1944C>T		intron	N/A
	ENSG00000293605	ENST00000715806.1		n.662-4171C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152080 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00165 AC: 253 AN: 153638 AF XY: 0.00141

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00985

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000918

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000170

Gnomad OTH exome AF: 0.000922

GnomAD4 exome AF: 0.000268 AC: 375 AN: 1397172 Hom.: 3 Cov.: 32 AF XY: 0.000260 AC XY: 179 AN XY: 689118

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

American (AMR) AF: 0.00821 AC: 293 AN: 35696

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

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35738

South Asian (SAS) AF: 0.000164 AC: 13 AN: 79140

European-Finnish (FIN) AF: 0.0000406 AC: 2 AN: 49216

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

European-Non Finnish (NFE) AF: 0.0000510 AC: 55 AN: 1078798

Other (OTH) AF: 0.000173 AC: 10 AN: 57814

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152196 Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20 AN XY: 74414

African (AFR) AF: 0.0000963 AC: 4 AN: 41528

American (AMR) AF: 0.00196 AC: 30 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.000756

ExAC AF: 0.000110 AC: 3

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	0.33
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.58	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.68	T
PhyloP100		1.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
Sift	Benign	0.067	T
Sift4G	Uncertain	0.0020	D
Vest4		0.45
MVP		0.56
ClinPred		0.049	T
GERP RS		2.4
PromoterAI		-0.015	Neutral
Varity_R		0.085
gMVP		0.30
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;