chr21-14964811-G-A

Variant names:

• chr21-14964811-G-A
• NM_003489.4:c.3382C>T

Variant summary

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

The NM_003489.4(NRIP1):​c.3382C>T​(p.His1128Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H1128R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRIP1 NM_003489.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.10
• Publications: 0 publications found

Genes affected

NRIP1 (HGNC:8001): (nuclear receptor interacting protein 1) Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein modulates transcriptional activity of the estrogen receptor. [provided by RefSeq, Jul 2008]

ASMER1 (HGNC:53135): (adipocyte associated metabolic related lncRNA 1)

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=0.32093883).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003489.4. 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
	NRIP1	NM_003489.4	MANE Select	c.3382C>T	p.His1128Tyr	missense	Exon 4 of 4	NP_003480.2	P48552
	NRIP1	NM_001439275.1		c.3382C>T	p.His1128Tyr	missense	Exon 5 of 5	NP_001426204.1
	NRIP1	NM_001439276.1		c.3382C>T	p.His1128Tyr	missense	Exon 4 of 4	NP_001426205.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRIP1	ENST00000318948.7	TSL:2 MANE Select	c.3382C>T	p.His1128Tyr	missense	Exon 4 of 4	ENSP00000327213.4	P48552
	NRIP1	ENST00000400199.5	TSL:3	c.3382C>T	p.His1128Tyr	missense	Exon 3 of 3	ENSP00000383060.1	P48552
	NRIP1	ENST00000400202.5	TSL:5	c.3382C>T	p.His1128Tyr	missense	Exon 3 of 3	ENSP00000383063.1	P48552

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.22
Sift	Benign	0.042	D
Sift4G	Benign	0.66	T
Polyphen		0.97	D
Vest4		0.45
MutPred		0.20		Gain of phosphorylation at H1128 (P = 0.0304)
MVP		0.23
MPC		0.11
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.31
Mutation Taster		=84/16	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: chr21-16337132;