19-49646724-C-T

Variant names:

• chr19-49646724-C-T
• NM_021228.3:c.372C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_021228.3(SCAF1):​c.372C>T​(p.Asp124Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCAF1 NM_021228.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

Genes affected

SCAF1 (HGNC:30403): (SR-related CTD associated factor 1) Enables RNA polymerase II C-terminal domain binding activity. Predicted to be involved in RNA splicing; mRNA processing; and transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.61 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAF1	NM_021228.3	c.372C>T	p.Asp124Asp	synonymous_variant	Exon 6 of 11	ENST00000360565.8	NP_067051.2
SCAF1	XM_011527194.4	c.381C>T	p.Asp127Asp	synonymous_variant	Exon 6 of 11		XP_011525496.1
SCAF1	XM_005259122.6	c.372C>T	p.Asp124Asp	synonymous_variant	Exon 6 of 11		XP_005259179.1
SCAF1	XM_017027083.3	c.102C>T	p.Asp34Asp	synonymous_variant	Exon 3 of 8		XP_016882572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAF1	ENST00000360565.8	c.372C>T	p.Asp124Asp	synonymous_variant	Exon 6 of 11	2	NM_021228.3	ENSP00000353769.2
SCAF1	ENST00000598359.5	c.372C>T	p.Asp124Asp	synonymous_variant	Exon 6 of 7	3		ENSP00000473210.1
SCAF1	ENST00000595242.3	c.*105C>T		downstream_gene_variant		3		ENSP00000472276.1
SCAF1	ENST00000601038.5	c.*166C>T		downstream_gene_variant		3		ENSP00000472649.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461662 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Benign	0.70
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50149981;