19-39453491-C-G

Variant names:

• chr19-39453491-C-G
• rs777349140
• NM_001111020.3:c.211C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001111020.3(SUPT5H):​c.211C>G​(p.Arg71Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SUPT5H NM_001111020.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33729005).

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.211C>G	p.Arg71Gly	missense	Exon 3 of 30	NP_001104490.1	O00267-1
	SUPT5H	NM_001130824.2		c.211C>G	p.Arg71Gly	missense	Exon 3 of 30	NP_001124296.1	O00267-1
	SUPT5H	NM_001319990.2		c.211C>G	p.Arg71Gly	missense	Exon 3 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.211C>G	p.Arg71Gly	missense	Exon 3 of 30	ENSP00000404029.4	O00267-1
	SUPT5H	ENST00000598725.5	TSL:1	c.211C>G	p.Arg71Gly	missense	Exon 2 of 29	ENSP00000469090.1	O00267-1
	SUPT5H	ENST00000359191.10	TSL:1	c.211C>G	p.Arg71Gly	missense	Exon 2 of 28	ENSP00000352117.6	O00267-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.73
MVP		0.61
MPC		1.2
ClinPred		0.94	D
GERP RS		3.5
Varity_R		0.47
gMVP		0.21
Mutation Taster		=87/13	polymorphism

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: rs777349140; hg19: chr19-39944131;