chr19-39458854-G-A

Position:

• chr19-39458854-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001111020.3(SUPT5H):​c.356G>A​(p.Arg119His) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUPT5H NM_001111020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21485785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT5H	NM_001111020.3	c.356G>A	p.Arg119His	missense_variant	6/30	ENST00000432763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT5H	ENST00000432763.7	c.356G>A	p.Arg119His	missense_variant	6/30	1	NM_001111020.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461412 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726936

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.356G>A (p.R119H) alteration is located in exon 5 (coding exon 5) of the SUPT5H gene. This alteration results from a G to A substitution at nucleotide position 356, causing the arginine (R) at amino acid position 119 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T;T;.;.;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.15
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	.;D;D;.;.;D
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.21	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;.;.;N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.15	.;N;N;.;.;.
REVEL	Uncertain	0.30
Sift	Benign	0.22	.;T;T;.;.;.
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.0070	B;B;B;B;B;.
Vest4		0.18
MutPred		0.36		Loss of MoRF binding (P = 0.0114);Loss of MoRF binding (P = 0.0114);.;.;Loss of MoRF binding (P = 0.0114);.;
MVP		0.34
MPC		1.1
ClinPred		0.80	D
GERP RS		5.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.078
gMVP		0.064

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: chr19-39949494;