NM_017736.5:c.743G>T

Variant names:

• chr16-20737199-C-A
• NM_017736.5:c.743G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017736.5(THUMPD1):​c.743G>T​(p.Cys248Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: THUMPD1 NM_017736.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• Publications: 0 publications found

Genes affected

THUMPD1 (HGNC:23807): (THUMP domain containing 1) Enables RNA binding activity. Predicted to be involved in tRNA modification. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACSM3 (HGNC:10522): (acyl-CoA synthetase medium chain family member 3) Enables butyrate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. Implicated in IgA glomerulonephritis. Biomarker of ulcerative colitis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017736.5. 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
	THUMPD1	NM_017736.5	MANE Select	c.743G>T	p.Cys248Phe	missense	Exon 4 of 4	NP_060206.2
	THUMPD1	NM_001304550.2		c.743G>T	p.Cys248Phe	missense	Exon 4 of 5	NP_001291479.1	Q9NXG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	THUMPD1	ENST00000396083.7	TSL:1 MANE Select	c.743G>T	p.Cys248Phe	missense	Exon 4 of 4	ENSP00000379392.2	Q9NXG2
	THUMPD1	ENST00000381337.6	TSL:1	c.743G>T	p.Cys248Phe	missense	Exon 4 of 5	ENSP00000370741.2	Q9NXG2
	THUMPD1	ENST00000888379.1		c.743G>T	p.Cys248Phe	missense	Exon 4 of 5	ENSP00000558438.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-10	D
REVEL	Uncertain	0.54
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.77		Loss of sheet (P = 0.0817)
MVP		0.93
MPC		0.91
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.96
gMVP		0.80

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: chr16-20748521;