1-35186362-G-T

Variant names:

• chr1-35186362-G-T
• rs10493067
• NM_005066.3:c.1986+639C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005066.3(SFPQ):​c.1986+639C>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SFPQ NM_005066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• Publications: 6 publications found

Genes affected

SFPQ (HGNC:10774): (splicing factor proline and glutamine rich) Enables DNA binding activity; histone deacetylase binding activity; and protein homodimerization activity. Involved in several processes, including alternative mRNA splicing, via spliceosome; positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; and regulation of transcription by RNA polymerase II. Acts upstream of or within double-strand break repair via homologous recombination. Located in chromatin; nuclear matrix; and paraspeckles. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.64).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005066.3. 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
	SFPQ	NM_005066.3	MANE Select	c.1986+639C>A		intron	N/A	NP_005057.1
	SFPQ	NR_136702.2		n.2082+639C>A		intron	N/A
	SFPQ	NR_136703.2		n.2094+639C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFPQ	ENST00000357214.6	TSL:1 MANE Select	c.1986+639C>A		intron	N/A	ENSP00000349748.5
	SFPQ	ENST00000696553.1		c.2049+639C>A		intron	N/A	ENSP00000512713.1
	SFPQ	ENST00000460428.5	TSL:2	n.240+639C>A		intron	N/A	ENSP00000425071.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.50
PhyloP100		0.52

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: rs10493067; hg19: chr1-35651963;