13-44943622-A-T

Variant names:

• chr13-44943622-A-T
• rs61742037
• NM_012345.3:c.1191T>A

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_012345.3(NUFIP1):​c.1191T>A​(p.Asp397Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000825 in 1,614,002 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (5 hom.)
• Consequence: NUFIP1 NM_012345.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.116
• Publications: 1 publications found

Genes affected

NUFIP1 (HGNC:8057): (nuclear FMR1 interacting protein 1) This gene encodes a nuclear RNA binding protein that contains a C2H2 zinc finger motif and a nuclear localization signal. This protein is associated with the nuclear matrix in perichromatin fibrils and, in neurons, localizes to the cytoplasm in association with endoplasmic reticulum ribosomes. This protein interacts with the fragile X mental retardation protein (FMRP), the tumor suppressor protein BRCA1, upregulates RNA polymerase II transcription, and is involved in box C/D snoRNP biogenesis. A pseudogene of this gene resides on chromosome 6q12. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030132234).
• BP6: Variant 13-44943622-A-T is Benign according to our data. Variant chr13-44943622-A-T is described in ClinVar as Benign. ClinVar VariationId is 787107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012345.3. 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
	NUFIP1	NM_012345.3	MANE Select	c.1191T>A	p.Asp397Glu	missense	Exon 9 of 10	NP_036477.2	Q9UHK0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUFIP1	ENST00000379161.5	TSL:1 MANE Select	c.1191T>A	p.Asp397Glu	missense	Exon 9 of 10	ENSP00000368459.4	Q9UHK0

Frequencies

GnomAD3 genomes AF: 0.00427 AC: 650 AN: 152216 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00117 AC: 295 AN: 251268 AF XY: 0.000847

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000465 AC: 679 AN: 1461668 Hom.: 5 Cov.: 31 AF XY: 0.000381 AC XY: 277 AN XY: 727120

African (AFR) AF: 0.0134 AC: 450 AN: 33464

American (AMR) AF: 0.000985 AC: 44 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111958

Other (OTH) AF: 0.00106 AC: 64 AN: 60380

GnomAD4 genome AF: 0.00428 AC: 652 AN: 152334 Hom.: 2 Cov.: 32 AF XY: 0.00428 AC XY: 319 AN XY: 74500

African (AFR) AF: 0.0145 AC: 604 AN: 41588

American (AMR) AF: 0.00157 AC: 24 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68018

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.000670 Hom.: 0

Bravo AF: 0.00519

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00141 AC: 171

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.23
DANN	Benign	0.20
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.12
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.41	N
REVEL	Benign	0.039
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0090	B
Vest4		0.065
MutPred		0.17		Gain of catalytic residue at N393 (P = 0.0342)
MVP		0.47
MPC		0.046
ClinPred		0.0024	T
GERP RS		-1.4
Varity_R		0.022
gMVP		0.093
Mutation Taster		=99/1	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: rs61742037; hg19: chr13-45517757;