12-31981112-C-A

Variant names:

• chr12-31981112-C-A
• rs1939773778
• NM_018169.4:c.157C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018169.4(RESF1):​c.157C>A​(p.Pro53Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RESF1 NM_018169.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.637

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035245568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RESF1	NM_018169.4	c.157C>A	p.Pro53Thr	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.157C>A	p.Pro53Thr	missense_variant	Exon 4 of 6	1	NM_018169.4	ENSP00000310338.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157C>A (p.P53T) alteration is located in exon 4 (coding exon 1) of the KIAA1551 gene. This alteration results from a C to A substitution at nucleotide position 157, causing the proline (P) at amino acid position 53 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.4
DANN	Benign	0.63
DEOGEN2	Benign	0.015	T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.025
Sift	Benign	0.13	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.24	B;.
Vest4		0.087
MutPred		0.23		Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);
MVP		0.092
MPC		0.011
ClinPred		0.095	T
GERP RS		-0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.050
gMVP		0.11

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: rs1939773778; hg19: chr12-32134046;