chr7-6330775-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM220A	NM_001037163.2	c.380G>A	p.Arg127Gln	missense_variant	Exon 2 of 2	ENST00000313324.9	NP_001032240.1
SMIM10L3	NM_001395995.1	c.*440G>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000578372.2	NP_001382924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM220A	ENST00000313324.9	c.380G>A	p.Arg127Gln	missense_variant	Exon 2 of 2	1	NM_001037163.2	ENSP00000317289.4
SAGSIN1	ENST00000578372	c.*440G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001395995.1	ENSP00000464009.1
FAM220A	ENST00000524898.1	c.*20G>A		downstream_gene_variant		3		ENSP00000432444.2
FAM220A	ENST00000530143.1	c.*53G>A		downstream_gene_variant		4		ENSP00000436886.2

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

GnomAD3 exomes AF: 0.591 AC: 148511 AN: 251270 Hom.: 46842 AF XY: 0.581 AC XY: 78961 AN XY: 135828

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 SAS exome AF: 0.665

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

Gnomad4 AFR exome AF: 0.835

Gnomad4 AMR exome AF: 0.717

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.908

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.547

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

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.504

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.585

Alfa AF: 0.492 Hom.: 10094

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 v4.3

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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.59	N;.
REVEL	Benign	0.11
Sift	Benign	0.60	T;.
Sift4G	Benign	0.54	T;T
Polyphen		0.99	D;D
Vest4		0.046
MPC		0.026
ClinPred		0.026	T
GERP RS		4.2
Varity_R		0.037
gMVP		0.067

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3750040; hg19: chr7-6370406; COSMIC: COSV57627208; COSMIC: COSV57627208;