dbSNP rs3750040: FAM220A:p.Arg127Leu (chr7-6330775-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037163.2(FAM220A):c.380G>T(p.Arg127Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FAM220A
NM_001037163.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

28 publications found

Variant links:

Genes affected

FAM220A (HGNC:22422): (family with sequence similarity 220 member A) Predicted to enable STAT family protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II and protein dephosphorylation. Predicted to act upstream of or within positive regulation of protein binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM220A links:

SMIM10L3 (HGNC:56768):

SMIM10L3 links:

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ACMG classification

Classification was made for transcript

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=0.13827291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM220A	NM_001037163.2 link	c.380G>T	p.Arg127Leu	missense_variant	Exon 2 of 2	ENST00000313324.9	NP_001032240.1
SMIM10L3	NM_001395995.1 link	c.*440G>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000578372.2	NP_001382924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAM220A	ENST00000313324.9 link	c.380G>T	p.Arg127Leu	missense_variant	Exon 2 of 2	1	NM_001037163.2	ENSP00000317289.4	Q7Z4H9
SMIM10L3	ENST00000578372.2 link	c.*440G>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001395995.1	ENSP00000464009.1	A0A0C4DGP1
FAM220A	ENST00000524898.2 link	c.380G>T	p.Arg127Leu	missense_variant	Exon 2 of 2	3		ENSP00000432444.2	E9PQY0
FAM220A	ENST00000530143.2 link	c.380G>T	p.Arg127Leu	missense_variant	Exon 2 of 2	4		ENSP00000436886.2	E9PQC6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251270

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.4

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.00037

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;N

PhyloP100

0.60

PrimateAI

Benign

0.31

PROVEAN

Benign

0.96

N;.

REVEL

Benign

0.081

Sift

Benign

0.31

T;.

Sift4G

Benign

0.36

T;T

Polyphen

0.61

P;P

Vest4

0.27

MutPred

0.30

Loss of solvent accessibility (P = 0.0079);Loss of solvent accessibility (P = 0.0079);

MVP

0.29

MPC

0.030

ClinPred

0.34

GERP RS

4.2

Varity_R

0.079

gMVP

0.065

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over