chr7-6330775-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037163.2(FAM220A):​c.380G>A​(p.Arg127Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,613,848 control chromosomes in the GnomAD database, including 237,434 homozygotes. 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.

• Frequency:
  • Genomes: 𝑓 0.61 (30547 hom., cov: 31)
  • Exomes 𝑓: 0.52 (206887 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.199287E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

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>A	p.Arg127Gln	missense	Exon 2 of 2	NP_001032240.1	Q7Z4H9
	SMIM10L3	NM_001395995.1	MANE Select	c.*440G>A		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>A	p.Arg127Gln	missense	Exon 2 of 2	ENSP00000317289.4	Q7Z4H9
	SMIM10L3	ENST00000578372.2	TSL:1 MANE Select	c.*440G>A		3_prime_UTR	Exon 2 of 2	ENSP00000464009.1	A0A0C4DGP1
	FAM220A	ENST00000524898.2	TSL:3	c.380G>A	p.Arg127Gln	missense	Exon 2 of 2	ENSP00000432444.2	Q7Z4H9

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93098 AN: 151864 Hom.: 30501 Cov.: 31

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.578

GnomAD2 exomes AF: 0.591 AC: 148511 AN: 251270 AF XY: 0.581

Gnomad AFR exome AF: 0.827

Gnomad AMR exome AF: 0.726

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.476

Gnomad OTH exome AF: 0.551

GnomAD4 exome AF: 0.521 AC: 761516 AN: 1461866 Hom.: 206887 Cov.: 76 AF XY: 0.522 AC XY: 379750 AN XY: 727228

African (AFR) AF: 0.835 AC: 27947 AN: 33480

American (AMR) AF: 0.717 AC: 32061 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 12025 AN: 26136

East Asian (EAS) AF: 0.908 AC: 36030 AN: 39700

South Asian (SAS) AF: 0.662 AC: 57139 AN: 86258

European-Finnish (FIN) AF: 0.506 AC: 27025 AN: 53416

Middle Eastern (MID) AF: 0.496 AC: 2859 AN: 5768

European-Non Finnish (NFE) AF: 0.480 AC: 533371 AN: 1111990

Other (OTH) AF: 0.547 AC: 33059 AN: 60394

GnomAD4 genome AF: 0.613 AC: 93205 AN: 151982 Hom.: 30547 Cov.: 31 AF XY: 0.618 AC XY: 45862 AN XY: 74252

African (AFR) AF: 0.821 AC: 34072 AN: 41498

American (AMR) AF: 0.658 AC: 10033 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1575 AN: 3466

East Asian (EAS) AF: 0.898 AC: 4632 AN: 5158

South Asian (SAS) AF: 0.671 AC: 3229 AN: 4812

European-Finnish (FIN) AF: 0.504 AC: 5312 AN: 10548

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32440 AN: 67946

Other (OTH) AF: 0.585 AC: 1235 AN: 2112

Alfa AF: 0.521 Hom.: 16724

Bravo AF: 0.635

TwinsUK AF: 0.484 AC: 1796

ALSPAC AF: 0.493 AC: 1901

ESP6500AA AF: 0.815 AC: 3590

ESP6500EA AF: 0.477 AC: 4105

ExAC AF: 0.588 AC: 71385

Asia WGS AF: 0.821 AC: 2856 AN: 3478

EpiCase AF: 0.482

EpiControl AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.7
DANN	Benign	0.68
DEOGEN2	Benign	0.00052	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.60
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.11
Sift	Benign	0.60	T
Sift4G	Benign	0.54	T
Polyphen		0.99	D
Vest4		0.046
MPC		0.026
ClinPred		0.026	T
GERP RS		4.2
Varity_R		0.037
gMVP		0.067
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV57627208; COSMIC: COSV57627208;