chr19-39459949-T-C

Position:

• chr19-39459949-T-C

Variant summary

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

The NM_001111020.3(SUPT5H):​c.613T>C​(p.Phe205Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SUPT5H NM_001111020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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=0.24178803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SUPT5H	NM_001111020.3	c.613T>C	p.Phe205Leu	missense_variant	10/30	ENST00000432763.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SUPT5H	ENST00000432763.7	c.613T>C	p.Phe205Leu	missense_variant	10/30	1	NM_001111020.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000227

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

Sep 22, 2022

The c.613T>C (p.F205L) alteration is located in exon 9 (coding exon 9) of the SUPT5H gene. This alteration results from a T to C substitution at nucleotide position 613, causing the phenylalanine (F) at amino acid position 205 to be replaced by a leucine (L). 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	Pathogenic	0.89
BayesDel_addAF	Benign	0.0059	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T;T;.;.;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.068
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	.;D;D;.;.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L;L;.;.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.8	.;N;N;.;.;.
REVEL	Benign	0.19
Sift	Benign	0.62	.;T;T;.;.;.
Sift4G	Benign	0.62	T;T;T;T;T;T
Polyphen		0.024	B;B;B;B;B;.
Vest4		0.37
MutPred		0.34		Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;Gain of sheet (P = 0.0827);.;
MVP		0.45
MPC		1.1
ClinPred		0.56	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs1421856185; hg19: chr19-39950589;