chr19-10089985-C-A

Variant names:

• chr19-10089985-C-A
• NM_018381.4:c.322C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_018381.4(SHFL):​c.322C>A​(p.Arg108Arg) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SHFL NM_018381.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.704
• 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]

ENSG00000267387 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 19-10089985-C-A is Benign according to our data. Variant chr19-10089985-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3772183.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.704 with no splicing effect.

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.322C>A	p.Arg108Arg	synonymous	Exon 5 of 8	NP_060851.2	Q9NUL5-1
	SHFL	NM_001308277.2		c.322C>A	p.Arg108Arg	synonymous	Exon 5 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.322C>A	p.Arg108Arg	synonymous	Exon 5 of 8	ENSP00000253110.10	Q9NUL5-1
	SHFL	ENST00000591813.5	TSL:1	c.322C>A	p.Arg108Arg	synonymous	Exon 5 of 8	ENSP00000467182.1	Q9NUL5-4
	SHFL	ENST00000971497.1		c.586C>A	p.Arg196Arg	synonymous	Exon 6 of 9	ENSP00000641556.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		0.70
PromoterAI		0.030	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr19-10200661; COSMIC: COSV53461652; COSMIC: COSV53461652;