15-66337167-T-C

Variant names:

• chr15-66337167-T-C
• rs1360379047
• NM_017858.3:c.697A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_017858.3(TIPIN):​c.697A>G​(p.Thr233Ala) 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. 15/21 in silico tools predict 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIPIN NM_017858.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

Genes affected

TIPIN (HGNC:30750): (TIMELESS interacting protein) The protein encoded by this gene is part of the replisome complex, a group of proteins that support DNA replication. It binds TIM, which is involved in circadian rhythm regulation, and aids in protecting cells against DNA damage and stress. Two pseudogenes and two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a modified_residue Phosphothreonine (size 0) in uniprot entity TIPIN_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05942121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIPIN	NM_017858.3	c.697A>G	p.Thr233Ala	missense_variant	Exon 8 of 8	ENST00000261881.9	NP_060328.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIPIN	ENST00000261881.9	c.697A>G	p.Thr233Ala	missense_variant	Exon 8 of 8	1	NM_017858.3	ENSP00000261881.4
TIPIN	ENST00000562124.5	c.697A>G	p.Thr233Ala	missense_variant	Exon 8 of 8	5		ENSP00000457406.1
TIPIN	ENST00000566524.5	n.*396A>G		non_coding_transcript_exon_variant	Exon 7 of 7	2		ENSP00000455656.1
TIPIN	ENST00000566524.5	n.*396A>G		3_prime_UTR_variant	Exon 7 of 7	2		ENSP00000455656.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461166 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Benign	0.51
DEOGEN2	Benign	0.0042	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.027
Sift	Benign	0.067	T;T
Sift4G	Benign	0.74	T;.
Polyphen		0.0020	B;.
Vest4		0.077
MutPred		0.092		Loss of glycosylation at T233 (P = 0.0357);Loss of glycosylation at T233 (P = 0.0357);
MVP		0.055
MPC		0.095
ClinPred		0.071	T
GERP RS		-0.52
Varity_R		0.028
gMVP		0.097

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: rs1360379047; hg19: chr15-66629505;