chr19-39466551-C-G

Position:

• chr19-39466551-C-G

Variant summary

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

The NM_001111020.3(SUPT5H):​c.948C>G​(p.Ile316Met) variant causes a missense change. 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: SUPT5H NM_001111020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03

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]

SUPT5H (HGNC:):

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=0.2591786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUPT5H	NM_001111020.3	c.948C>G	p.Ile316Met	missense_variant	12/30	ENST00000432763.7	NP_001104490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUPT5H	ENST00000432763.7	c.948C>G	p.Ile316Met	missense_variant	12/30	1	NM_001111020.3	ENSP00000404029.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 05, 2024

The c.948C>G (p.I316M) alteration is located in exon 11 (coding exon 11) of the SUPT5H gene. This alteration results from a C to G substitution at nucleotide position 948, causing the isoleucine (I) at amino acid position 316 to be replaced by a methionine (M). 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	0.24
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.033	T;T;.;.;T;T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	.;D;D;.;.;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.26	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.43	N;N;.;.;N;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.93	.;N;N;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.27	.;T;T;.;.;.
Sift4G	Benign	0.40	T;T;T;T;T;T
Polyphen		0.019	B;B;B;B;B;.
Vest4		0.71
MutPred		0.42		Gain of disorder (P = 0.0326);Gain of disorder (P = 0.0326);.;.;Gain of disorder (P = 0.0326);.;
MVP		0.60
MPC		0.95
ClinPred		0.73	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr19-39957191;