12-31981394-C-T

Variant names:

• chr12-31981394-C-T
• rs61353224
• NM_018169.4:c.439C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018169.4(RESF1):​c.439C>T​(p.Pro147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,613,988 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (70 hom.)
• Consequence: RESF1 NM_018169.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.647

Genes affected

RESF1 (HGNC:25559): (retroelement silencing factor 1) Predicted to enable histone binding activity and histone methyltransferase binding activity. Predicted to be involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate and positive regulation of DNA methylation-dependent heterochromatin assembly. Predicted to act upstream of or within response to bacterium. Predicted to be located in nucleus. Predicted to colocalize with gamma-tubulin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027252436).
• BP6: Variant 12-31981394-C-T is Benign according to our data. Variant chr12-31981394-C-T is described in ClinVar as [Benign]. Clinvar id is 786225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RESF1	NM_018169.4	c.439C>T	p.Pro147Ser	missense_variant	Exon 4 of 6	ENST00000312561.9	NP_060639.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RESF1	ENST00000312561.9	c.439C>T	p.Pro147Ser	missense_variant	Exon 4 of 6	1	NM_018169.4	ENSP00000310338.4

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2358 AN: 152146 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00426 AC: 1070 AN: 251230 AF XY: 0.00314

Gnomad AFR exome AF: 0.0591

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00163 AC: 2377 AN: 1461724 Hom.: 70 Cov.: 44 AF XY: 0.00137 AC XY: 996 AN XY: 727164

Gnomad4 AFR exome AF: 0.0578 AC: 1935 AN: 33480

Gnomad4 AMR exome AF: 0.00288 AC: 129 AN: 44716

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26132

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39696

Gnomad4 SAS exome AF: 0.0000580 AC: 5 AN: 86254

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53380

Gnomad4 NFE exome AF: 0.0000675 AC: 75 AN: 1111908

Gnomad4 Remaining exome AF: 0.00359 AC: 217 AN: 60392

GnomAD4 genome AF: 0.0156 AC: 2368 AN: 152264 Hom.: 64 Cov.: 32 AF XY: 0.0149 AC XY: 1111 AN XY: 74456

Gnomad4 AFR AF: 0.0542 AC: 0.0541861 AN: 0.0541861

Gnomad4 AMR AF: 0.00543 AC: 0.00542767 AN: 0.00542767

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000147 AC: 0.000147042 AN: 0.000147042

Gnomad4 OTH AF: 0.0109 AC: 0.0108798 AN: 0.0108798

Alfa AF: 0.00622 Hom.: 43

Bravo AF: 0.0179

ESP6500AA AF: 0.0508 AC: 224

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00521 AC: 633

Asia WGS AF: 0.00491 AC: 18 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.98
DANN	Benign	0.80
DEOGEN2	Benign	0.048	T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.54	T;T
MetaRNN	Benign	0.0027	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.18	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.061
Sift	Benign	0.13	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.093	B;.
Vest4		0.10
MVP		0.099
MPC		0.014
ClinPred		0.010	T
GERP RS		1.1
Varity_R		0.037
gMVP		0.16
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs61353224; hg19: chr12-32134328;