19-39464893-G-A

Variant names:

• chr19-39464893-G-A
• rs2304217
• NM_001111020.3:c.720G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001111020.3(SUPT5H):​c.720G>A​(p.Glu240Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 1,614,046 control chromosomes in the GnomAD database, including 23,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2046 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21256 hom.)
• Consequence: SUPT5H NM_001111020.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.44
• Publications: 21 publications found

Genes affected

SUPT5H (HGNC:11469): (SPT5 homolog, DSIF elongation factor subunit) Enables enzyme binding activity and protein heterodimerization activity. Involved in positive regulation of macroautophagy; regulation of RNA metabolic process; and transcription elongation from RNA polymerase II promoter. Located in nucleoplasm. Part of DSIF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 19-39464893-G-A is Benign according to our data. Variant chr19-39464893-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.44 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111020.3. 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
	SUPT5H	NM_001111020.3	MANE Select	c.720G>A	p.Glu240Glu	synonymous	Exon 11 of 30	NP_001104490.1	O00267-1
	SUPT5H	NM_001130824.2		c.720G>A	p.Glu240Glu	synonymous	Exon 11 of 30	NP_001124296.1	O00267-1
	SUPT5H	NM_001319990.2		c.720G>A	p.Glu240Glu	synonymous	Exon 11 of 30	NP_001306919.1	O00267-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUPT5H	ENST00000432763.7	TSL:1 MANE Select	c.720G>A	p.Glu240Glu	synonymous	Exon 11 of 30	ENSP00000404029.4	O00267-1
	SUPT5H	ENST00000598725.5	TSL:1	c.720G>A	p.Glu240Glu	synonymous	Exon 10 of 29	ENSP00000469090.1	O00267-1
	SUPT5H	ENST00000359191.10	TSL:1	c.708G>A	p.Glu236Glu	synonymous	Exon 9 of 28	ENSP00000352117.6	O00267-2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24535 AN: 152056 Hom.: 2046 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.148

GnomAD2 exomes AF: 0.146 AC: 36808 AN: 251420 AF XY: 0.146

Gnomad AFR exome AF: 0.156

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.0989

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.168 AC: 245590 AN: 1461872 Hom.: 21256 Cov.: 34 AF XY: 0.167 AC XY: 121257 AN XY: 727238

African (AFR) AF: 0.150 AC: 5016 AN: 33480

American (AMR) AF: 0.118 AC: 5285 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 3552 AN: 26136

East Asian (EAS) AF: 0.0934 AC: 3708 AN: 39700

South Asian (SAS) AF: 0.110 AC: 9472 AN: 86258

European-Finnish (FIN) AF: 0.179 AC: 9569 AN: 53420

Middle Eastern (MID) AF: 0.120 AC: 695 AN: 5768

European-Non Finnish (NFE) AF: 0.179 AC: 198558 AN: 1111992

Other (OTH) AF: 0.161 AC: 9735 AN: 60394

GnomAD4 genome AF: 0.161 AC: 24530 AN: 152174 Hom.: 2046 Cov.: 32 AF XY: 0.160 AC XY: 11879 AN XY: 74384

African (AFR) AF: 0.156 AC: 6494 AN: 41516

American (AMR) AF: 0.142 AC: 2170 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 463 AN: 3460

East Asian (EAS) AF: 0.106 AC: 549 AN: 5172

South Asian (SAS) AF: 0.112 AC: 539 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1902 AN: 10584

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11881 AN: 68012

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.160 Hom.: 4392

Bravo AF: 0.155

Asia WGS AF: 0.126 AC: 442 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.167

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	8.2
DANN	Benign	0.52
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2304217; hg19: chr19-39955533; COSMIC: COSV63238750; COSMIC: COSV63238750;