chr19-10091332-C-A

Variant names:

• chr19-10091332-C-A
• rs746145785
• NM_018381.4:c.467C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018381.4(SHFL):​c.467C>A​(p.Pro156Gln) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SHFL NM_018381.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.09
• Publications: 0 publications found

Genes affected

SHFL (HGNC:25649): (shiftless antiviral inhibitor of ribosomal frameshifting) This gene is an interferon stimulated gene (ISG) that inhibits viral replication. The encoded protein binds nucleic acids and inhibits programmed -1 ribosomal frameshifting required for translation by many RNA viruses. Viruses inhibited by the protein include Zika virus, dengue virus and the coronaviruses, SARS-CoV and SARS-CoV2. [provided by RefSeq, Aug 2021]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4009729).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018381.4. 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
	SHFL	NM_018381.4	MANE Select	c.467C>A	p.Pro156Gln	missense	Exon 6 of 8	NP_060851.2	Q9NUL5-1
	SHFL	NM_001308277.2		c.467C>A	p.Pro156Gln	missense	Exon 6 of 8	NP_001295206.1	Q9NUL5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHFL	ENST00000253110.16	TSL:2 MANE Select	c.467C>A	p.Pro156Gln	missense	Exon 6 of 8	ENSP00000253110.10	Q9NUL5-1
	SHFL	ENST00000591813.5	TSL:1	c.467C>A	p.Pro156Gln	missense	Exon 6 of 8	ENSP00000467182.1	Q9NUL5-4
	SHFL	ENST00000971497.1		c.731C>A	p.Pro244Gln	missense	Exon 7 of 9	ENSP00000641556.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.00099	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.14
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.86	T
PhyloP100		1.1
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.26
Sift	Benign	0.089	T
Sift4G	Benign	0.16	T
Vest4		0.56
MutPred		0.41		Gain of solvent accessibility (P = 0.0137)
MVP		0.43
MPC		1.4
ClinPred		0.97	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.64
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

dbSNP: rs746145785; hg19: chr19-10202008; COSMIC: COSV99463454; COSMIC: COSV99463454;