rs762108388

Variant names:

• chr7-150371299-C-T
• rs762108388
• NM_001099695.2:c.229C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001099695.2(REPIN1):​c.229C>T​(p.Leu77Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,590,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: REPIN1 NM_001099695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.03
• Publications: 1 publications found

Genes affected

REPIN1 (HGNC:17922): (replication initiator 1) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of glucose import and regulation of fatty acid transport. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF775 (HGNC:28501): (zinc finger protein 775) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

REPIN1-AS1 (HGNC:41201): (REPIN1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.033754647).
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099695.2. 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
	REPIN1	NM_001099695.2	MANE Select	c.229C>T	p.Leu77Phe	missense	Exon 3 of 3	NP_001093165.1	Q9BWE0-4
	REPIN1	NM_001388037.1		c.235C>T	p.Leu79Phe	missense	Exon 3 of 3	NP_001374966.1
	REPIN1	NM_001362745.2		c.229C>T	p.Leu77Phe	missense	Exon 3 of 3	NP_001349674.1	Q9BWE0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REPIN1	ENST00000489432.7	TSL:2 MANE Select	c.229C>T	p.Leu77Phe	missense	Exon 3 of 3	ENSP00000417291.2	Q9BWE0-4
	REPIN1	ENST00000444957.3	TSL:1	c.58C>T	p.Leu20Phe	missense	Exon 2 of 2	ENSP00000407714.1	Q9BWE0-3
	REPIN1	ENST00000466559.1	TSL:1	c.111C>T	p.Ser37Ser	synonymous	Exon 2 of 2	ENSP00000418507.1	C9J0L4

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000344 AC: 7 AN: 203710 AF XY: 0.0000270

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000198

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000194

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1438490 Hom.: 0 Cov.: 40 AF XY: 0.00000700 AC XY: 5 AN XY: 713956

African (AFR) AF: 0.00 AC: 0 AN: 33030

American (AMR) AF: 0.000193 AC: 8 AN: 41502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 38458

South Asian (SAS) AF: 0.00 AC: 0 AN: 83218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000454 AC: 5 AN: 1101418

Other (OTH) AF: 0.0000336 AC: 2 AN: 59522

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152328 Hom.: 0 Cov.: 34 AF XY: 0.0000940 AC XY: 7 AN XY: 74476

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.000849 AC: 13 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.0000250 AC: 3

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	Benign	0.085
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		-1.0
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.060
Sift	Benign	0.30	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.034
MutPred		0.38		Gain of glycosylation at S21 (P = 0.0776)
MVP		0.10
MPC		0.71
ClinPred		0.018	T
GERP RS		1.2
PromoterAI		-0.014	Neutral
Varity_R		0.055
gMVP		0.20
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762108388; hg19: chr7-150068388;