7-6330775-C-G

Variant names:

• chr7-6330775-C-G
• rs3750040
• NM_001037163.2:c.380G>C

Variant summary

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

The NM_001037163.2(FAM220A):​c.380G>C​(p.Arg127Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,924 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: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: FAM220A NM_001037163.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 28 publications found

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]

SMIM10L3 (HGNC:56768):

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=0.21647727).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037163.2. 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
	FAM220A	NM_001037163.2	MANE Select	c.380G>C	p.Arg127Pro	missense	Exon 2 of 2	NP_001032240.1	Q7Z4H9
	SMIM10L3	NM_001395995.1	MANE Select	c.*440G>C		3_prime_UTR	Exon 2 of 2	NP_001382924.1	A0A0C4DGP1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM220A	ENST00000313324.9	TSL:1 MANE Select	c.380G>C	p.Arg127Pro	missense	Exon 2 of 2	ENSP00000317289.4	Q7Z4H9
	SMIM10L3	ENST00000578372.2	TSL:1 MANE Select	c.*440G>C		3_prime_UTR	Exon 2 of 2	ENSP00000464009.1	A0A0C4DGP1
	FAM220A	ENST00000524898.2	TSL:3	c.380G>C	p.Arg127Pro	missense	Exon 2 of 2	ENSP00000432444.2	Q7Z4H9

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 76

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151924 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74170

African (AFR) AF: 0.00 AC: 0 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 16724

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.7
DANN	Benign	0.76
DEOGEN2	Benign	0.00018	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.60
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.16
Sift	Benign	0.28	T
Sift4G	Benign	0.26	T
Polyphen		0.99	D
Vest4		0.36
MutPred		0.18		Loss of MoRF binding (P = 0.0034)
MVP		0.13
MPC		0.038
ClinPred		0.22	T
GERP RS		4.2
Varity_R		0.17
gMVP		0.21
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3750040; hg19: chr7-6370406;