NM_021806.4:c.169T>C

Variant names:

• chrX-154508580-A-G
• rs781824027
• NM_021806.4:c.169T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_021806.4(FAM3A):​c.169T>C​(p.Tyr57His) variant causes a missense change. The variant allele was found at a frequency of 0.00000754 in 1,193,968 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000071 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: FAM3A NM_021806.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.67
• Publications: 0 publications found

Genes affected

FAM3A (HGNC:13749): (FAM3 metabolism regulating signaling molecule A) This gene encodes a cytokine-like protein. The expression of this gene may be regulated by peroxisome proliferator-activated receptor gamma, and the encoded protein may be involved in the regulation of glucose and lipid metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25550753).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021806.4. 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
	FAM3A	NM_021806.4	MANE Select	c.169T>C	p.Tyr57His	missense	Exon 4 of 9	NP_068578.2	P98173-1
	FAM3A	NM_001282311.2		c.211T>C	p.Tyr71His	missense	Exon 5 of 10	NP_001269240.1	D3DWX8
	FAM3A	NM_001363822.2		c.169T>C	p.Tyr57His	missense	Exon 5 of 10	NP_001350751.1	Q5HY75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM3A	ENST00000447601.7	TSL:1 MANE Select	c.169T>C	p.Tyr57His	missense	Exon 4 of 9	ENSP00000416146.2	P98173-1
	FAM3A	ENST00000858761.1		c.169T>C	p.Tyr57His	missense	Exon 4 of 9	ENSP00000528820.1
	FAM3A	ENST00000858759.1		c.217T>C	p.Tyr73His	missense	Exon 4 of 9	ENSP00000528818.1

Frequencies

GnomAD3 genomes AF: 0.0000708 AC: 8 AN: 113014 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 148275 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: 9.25e-7 AC: 1 AN: 1080954 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 351654

African (AFR) AF: 0.0000382 AC: 1 AN: 26173

American (AMR) AF: 0.00 AC: 0 AN: 32648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18946

East Asian (EAS) AF: 0.00 AC: 0 AN: 29587

South Asian (SAS) AF: 0.00 AC: 0 AN: 51691

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833418

Other (OTH) AF: 0.00 AC: 0 AN: 45477

GnomAD4 genome AF: 0.0000708 AC: 8 AN: 113014 Hom.: 0 Cov.: 24 AF XY: 0.000114 AC XY: 4 AN XY: 35166

African (AFR) AF: 0.000257 AC: 8 AN: 31141

American (AMR) AF: 0.00 AC: 0 AN: 10749

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3590

South Asian (SAS) AF: 0.00 AC: 0 AN: 2836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53291

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000168 AC: 2

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	0.34
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.7
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.15
Sift	Benign	0.36	T
Sift4G	Benign	0.47	T
Polyphen		0.037	B
Vest4		0.26
MVP		0.40
MPC		1.0
ClinPred		0.89	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.46
gMVP		0.65
Mutation Taster		=85/15	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: rs781824027; hg19: chrX-153736911;