NM_001099695.2:c.601C>T

Variant names:

• chr7-150371671-C-T
• rs751029113
• NM_001099695.2:c.601C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001099695.2(REPIN1):​c.601C>T​(p.Pro201Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000187 in 1,605,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: REPIN1 NM_001099695.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13383788).
• BS2: High AC in GnomAd4 at 17 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.601C>T	p.Pro201Ser	missense	Exon 3 of 3	NP_001093165.1	Q9BWE0-4
	REPIN1	NM_001388037.1		c.607C>T	p.Pro203Ser	missense	Exon 3 of 3	NP_001374966.1
	REPIN1	NM_001362745.2		c.601C>T	p.Pro201Ser	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.601C>T	p.Pro201Ser	missense	Exon 3 of 3	ENSP00000417291.2	Q9BWE0-4
	REPIN1	ENST00000444957.3	TSL:1	c.430C>T	p.Pro144Ser	missense	Exon 2 of 2	ENSP00000407714.1	Q9BWE0-3
	REPIN1	ENST00000466559.1	TSL:1	c.*315C>T		3_prime_UTR	Exon 2 of 2	ENSP00000418507.1	C9J0L4

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152264 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000335 AC: 8 AN: 239018 AF XY: 0.0000305

Gnomad AFR exome AF: 0.000472

Gnomad AMR exome AF: 0.0000292

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: 0.00

GnomAD4 exome AF: 0.00000895 AC: 13 AN: 1452882 Hom.: 0 Cov.: 68 AF XY: 0.00000968 AC XY: 7 AN XY: 723116

African (AFR) AF: 0.000329 AC: 11 AN: 33466

American (AMR) AF: 0.0000224 AC: 1 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26068

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111576

Other (OTH) AF: 0.0000166 AC: 1 AN: 60256

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152382 Hom.: 0 Cov.: 34 AF XY: 0.000107 AC XY: 8 AN XY: 74518

African (AFR) AF: 0.000385 AC: 16 AN: 41596

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

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

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.000121

ExAC AF: 0.0000165 AC: 2

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	Uncertain	0.48
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.017
Eigen_PC	Benign	-0.019
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.13
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.043	D
Polyphen		0.78	P
Vest4		0.30
MVP		0.28
MPC		1.2
ClinPred		0.18	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.56
Mutation Taster		=95/5	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: rs751029113; hg19: chr7-150068760;