NM_001111020.3:c.365C>A

Variant names:

• chr19-39458863-C-A
• NM_001111020.3:c.365C>A

Variant summary

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

The NM_001111020.3(SUPT5H):​c.365C>A​(p.Ala122Asp) 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: 5.97
• 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=0.29114115).

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.365C>A	p.Ala122Asp	missense	Exon 6 of 30	NP_001104490.1	O00267-1
	SUPT5H	NM_001130824.2		c.365C>A	p.Ala122Asp	missense	Exon 6 of 30	NP_001124296.1	O00267-1
	SUPT5H	NM_001319990.2		c.365C>A	p.Ala122Asp	missense	Exon 6 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.365C>A	p.Ala122Asp	missense	Exon 6 of 30	ENSP00000404029.4	O00267-1
	SUPT5H	ENST00000598725.5	TSL:1	c.365C>A	p.Ala122Asp	missense	Exon 5 of 29	ENSP00000469090.1	O00267-1
	SUPT5H	ENST00000359191.10	TSL:1	c.353C>A	p.Ala118Asp	missense	Exon 4 of 28	ENSP00000352117.6	O00267-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Benign	0.056	T
Sift4G	Benign	0.12	T
Polyphen		0.46	P
Vest4		0.70
MutPred		0.28		Loss of MoRF binding (P = 0.0299)
MVP		0.20
MPC		1.7
ClinPred		0.84	D
GERP RS		5.6
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.30
gMVP		0.43
Mutation Taster		=52/48	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

hg19: chr19-39949503;